49 results on '"Balwierz, Piotr"'
Search Results
2. Identification of novel potential interaction partners of UDP-galactose (SLC35A2), UDP-N-acetylglucosamine (SLC35A3) and an orphan (SLC35A4) nucleotide sugar transporters
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Wiktor, Maciej, Wiertelak, Wojciech, Maszczak-Seneczko, Dorota, Balwierz, Piotr Jan, Szulc, Bożena, and Olczak, Mariusz
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- 2021
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3. Germ cell differentiation requires Tdrd7-dependent chromatin and transcriptome reprogramming marked by germ plasm relocalization
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D’Orazio, Fabio M., Balwierz, Piotr J., González, Ada Jimenez, Guo, Yixuan, Hernández-Rodríguez, Benjamín, Wheatley, Lucy, Jasiulewicz, Aleksandra, Hadzhiev, Yavor, Vaquerizas, Juan M., Cairns, Bradley, Lenhard, Boris, and Müller, Ferenc
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- 2021
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4. Identification of downstream effectors of retinoic acid specifying the zebrafish pancreas by integrative genomics
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López-Pérez, Ana R., Balwierz, Piotr J., Lenhard, Boris, Muller, Ferenc, Wardle, Fiona C., Manfroid, Isabelle, Voz, Marianne L., and Peers, Bernard
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- 2021
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5. Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium
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Meier-Abt, Fabienne, Milani, Emanuela, Roloff, Tim, Brinkhaus, Heike, Duss, Stephan, Meyer, Dominique S, Klebba, Ina, Balwierz, Piotr J, van Nimwegen, Erik, and Bentires-Alj, Mohamed
- Abstract
Abstract Introduction Early pregnancy has a strong protective effect against breast cancer in humans and rodents, but the underlying mechanism is unknown. Because breast cancers are thought to arise from specific cell subpopulations of mammary epithelia, we studied the effect of parity on the transcriptome and the differentiation/proliferation potential of specific luminal and basal mammary cells in mice. Methods Mammary epithelial cell subpopulations (luminal Sca1-, luminal Sca1+, basal stem/progenitor, and basal myoepithelial cells) were isolated by flow cytometry from parous and age-matched virgin mice and examined by using a combination of unbiased genomics, bioinformatics, in vitro colony formation, and in vivo limiting dilution transplantation assays. Specific findings were further investigated with immunohistochemistry in entire glands of parous and age-matched virgin mice. Results Transcriptome analysis revealed an upregulation of differentiation genes and a marked decrease in the Wnt/Notch signaling ratio in basal stem/progenitor cells of parous mice. Separate bioinformatics analyses showed reduced activity for the canonical Wnt transcription factor LEF1/TCF7 and increased activity for the Wnt repressor TCF3. This finding was specific for basal stem/progenitor cells and was associated with downregulation of potentially carcinogenic pathways and a reduction in the proliferation potential of this cell subpopulation in vitro and in vivo. As a possible mechanism for decreased Wnt signaling in basal stem/progenitor cells, we found a more than threefold reduction in the expression of the secreted Wnt ligand Wnt4 in total mammary cells from parous mice, which corresponded to a similar decrease in the proportion of Wnt4-secreting and estrogen/progesterone receptor-positive cells. Because recombinant Wnt4 rescued the proliferation defect of basal stem/progenitor cells in vitro, reduced Wnt4 secretion appears to be causally related to parity-induced alterations of basal stem/progenitor cell properties in mice. Conclusions By revealing that parity induces differentiation and downregulates the Wnt/Notch signaling ratio and the in vitro and in vivo proliferation potential of basal stem/progenitor cells in mice, our study sheds light on the long-term consequences of an early pregnancy. Furthermore, it opens the door to future studies assessing whether inhibitors of the Wnt pathway may be used to mimic the parity-induced protective effect against breast cancer.
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- 2013
6. Amphioxus functional genomics and the origins of vertebrate gene regulation
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Marlétaz, Ferdinand, Firbas, Panos N., Maeso, Ignacio, Tena, Juan J., Bogdanovic, Ozren, Perry, Malcolm, Wyatt, Christopher D. R., de la Calle-Mustienes, Elisa, Bertrand, Stephanie, Burguera, Demian, Acemel, Rafael D., van Heeringen, Simon J., Naranjo, Silvia, Herrera-Ubeda, Carlos, Skvortsova, Ksenia, Jimenez-Gancedo, Sandra, Aldea, Daniel, Marquez, Yamile, Buono, Lorena, Kozmikova, Iryna, Permanyer, Jon, Louis, Alexandra, Albuixech-Crespo, Beatriz, Le Petillon, Yann, Leon, Anthony, Subirana, Lucie, Balwierz, Piotr J., Duckett, Paul Edward, Farahani, Ensieh, Aury, Jean-Marc, Mangenot, Sophie, Wincker, Patrick, Albalat, Ricard, Benito-Gutiérrez, Èlia, Cañestro, Cristian, Castro, Filipe, D’Aniello, Salvatore, Ferrier, David E. K., Huang, Shengfeng, Laudet, Vincent, Marais, Gabriel A. B., Pontarotti, Pierre, Schubert, Michael, Seitz, Hervé, Somorjai, Ildiko, Takahashi, Tokiharu, Mirabeau, Olivier, Xu, Anlong, Yu, Jr-Kai, Carninci, Piero, Martinez-Morales, Juan Ramon, Crollius, Hugues Roest, Kozmik, Zbynek, Weirauch, Matthew T., Garcia-Fernàndez, Jordi, Lister, Ryan, Lenhard, Boris, Holland, Peter W. H., Escriva, Hector, Gómez-Skarmeta, Jose Luis, and Irimia, Manuel
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- 2018
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7. Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing
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Nepal, Chirag, Hadzhiev, Yavor, Balwierz, Piotr, Tarifeño-Saldivia, Estefanía, Cardenas, Ryan, Wragg, Joseph W., Suzuki, Ana-Maria, Carninci, Piero, Peers, Bernard, Lenhard, Boris, Andersen, Jesper B., and Müller, Ferenc
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- 2020
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8. Transcription and enhancer profiling in human monocyte subsets
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Schmidl, Christian, Renner, Kathrin, Peter, Katrin, Eder, Ruediger, Lassmann, Timo, Balwierz, Piotr J., Itoh, Masayoshi, Nagao-Sato, Sayaka, Kawaji, Hideya, Carninci, Piero, Suzuki, Harukazu, Hayashizaki, Yoshihide, Andreesen, Reinhard, Hume, David A., Hoffmann, Petra, Forrest, Alistair R.R., Kreutz, Marina P., Edinger, Matthias, and Rehli, Michael
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- 2014
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9. The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations
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Schmidl, Christian, Hansmann, Leo, Lassmann, Timo, Balwierz, Piotr J., Kawaji, Hideya, Itoh, Masayoshi, Kawai, Jun, Nagao-Sato, Sayaka, Suzuki, Harukazu, Andreesen, Reinhard, Hayashizaki, Yoshihide, Forrest, Alistair R.R., Carninci, Piero, Hoffmann, Petra, Edinger, Matthias, and Rehli, Michael
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- 2014
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10. Sox4 Is a Master Regulator of Epithelial-Mesenchymal Transition by Controlling Ezh2 Expression and Epigenetic Reprogramming
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Tiwari, Neha, Tiwari, Vijay K., Waldmeier, Lorenz, Balwierz, Piotr J., Arnold, Phil, Pachkov, Mikhail, Meyer-Schaller, Nathalie, Schübeler, Dirk, van Nimwegen, Erik, and Christofori, Gerhard
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- 2013
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11. Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements
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European Commission, Agencia Estatal de Investigación (España), Baranasic, Damir, Hörtenhuber, Matthias, Balwierz, Piotr J., Zehnder, Tobias, Mukarram, Abdul Kadir, Nepal, Chirag, Várnai, Csilla, Hadzhiev, Yavor, Jiménez-González, Ada, Li, Nan, Wragg, Joseph, D’Orazio, Fabio M., Relic, Dorde, Pachkov, Mikhail, Díaz, Noelia, Hernández-Rodríguez, Benjamín, Chen, Zelin, Stoiber, Marcus, Dong, Michaël, Stevens, Irene, Ross, Samuel E., Eagle, Anne, Martin, Ryan, Obasaju, Oluwapelumi, Rastegar, Sepand, McGarvey, Alison C., Kopp, Wolfgang, Chambers, Emily, Wang, Dennis, Kim, Hyejeong R., Acemel, Rafael D., Naranjo, Silvia, Łapiński, Maciej, Chong, Vanessa, Mathavan, Sinnakaruppan, Peers, Bernard, Sauka-Spengler, Tatjana, Vingron, Martin, Carninci, Piero, Ohler, Uwe, Lacadie, Scott Allen, Burgess, Shawn M., Winata, Cecilia, Eeden, Freek van, Vaquerizas Erdocia, Juan Manuel, Gómez-Skarmeta, José Luis, Onichtchouk, Daria, Brown, Ben James, Bogdanovic, Ozren, Nimwegen, Erik van, Westerfield, Monte, Wardle, Fiona C., Daub, Carsten O., Lenhard, Boris, Müller, Ferenc, European Commission, Agencia Estatal de Investigación (España), Baranasic, Damir, Hörtenhuber, Matthias, Balwierz, Piotr J., Zehnder, Tobias, Mukarram, Abdul Kadir, Nepal, Chirag, Várnai, Csilla, Hadzhiev, Yavor, Jiménez-González, Ada, Li, Nan, Wragg, Joseph, D’Orazio, Fabio M., Relic, Dorde, Pachkov, Mikhail, Díaz, Noelia, Hernández-Rodríguez, Benjamín, Chen, Zelin, Stoiber, Marcus, Dong, Michaël, Stevens, Irene, Ross, Samuel E., Eagle, Anne, Martin, Ryan, Obasaju, Oluwapelumi, Rastegar, Sepand, McGarvey, Alison C., Kopp, Wolfgang, Chambers, Emily, Wang, Dennis, Kim, Hyejeong R., Acemel, Rafael D., Naranjo, Silvia, Łapiński, Maciej, Chong, Vanessa, Mathavan, Sinnakaruppan, Peers, Bernard, Sauka-Spengler, Tatjana, Vingron, Martin, Carninci, Piero, Ohler, Uwe, Lacadie, Scott Allen, Burgess, Shawn M., Winata, Cecilia, Eeden, Freek van, Vaquerizas Erdocia, Juan Manuel, Gómez-Skarmeta, José Luis, Onichtchouk, Daria, Brown, Ben James, Bogdanovic, Ozren, Nimwegen, Erik van, Westerfield, Monte, Wardle, Fiona C., Daub, Carsten O., Lenhard, Boris, and Müller, Ferenc
- Abstract
Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals
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- 2022
12. Integrated annotation and analysis of genomic features reveal new types of functional elements and large-scale epigenetic phenomena in the developing zebrafish
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Baranasic, Damir, primary, Hörtenhuber, Matthias, additional, Balwierz, Piotr, additional, Zehnder, Tobias, additional, Mukarram, Abdul Kadir, additional, Nepal, Chirag, additional, Varnai, Csilla, additional, Hadzhiev, Yavor, additional, Jimenez-Gonzalez, Ada, additional, Li, Nan, additional, Wragg, Joseph, additional, D’Orazio, Fabio, additional, Díaz, Noelia, additional, Hernández-Rodríguez, Benjamín, additional, Chen, Zelin, additional, Stoiber, Marcus, additional, Dong, Michaël, additional, Stevens, Irene, additional, Ross, Samuel E., additional, Eagle, Anne, additional, Martin, Ryan, additional, Obasaju, Pelumi, additional, Rastegar, Sepand, additional, McGarvey, Alison C., additional, Kopp, Wolfgang, additional, Chambers, Emily, additional, Wang, Dennis, additional, Kim, Hyejeong R., additional, Acemel, Rafael D., additional, Naranjo, Silvia, additional, Lapinski, Maciej, additional, Chong, Vanessa, additional, Mathavan, Sinnakaruppan, additional, Peers, Bernard, additional, Sauka-Spengler, Tatjana, additional, Vingron, Martin, additional, Carninci, Piero, additional, Ohler, Uwe, additional, Lacadie, Scott Allen, additional, Burgess, Shawn, additional, Winata, Cecilia, additional, van Eeden, Freek, additional, Vaquerizas, Juan M., additional, Gómez-Skarmeta, José Luis, additional, Onichtchouk, Daria, additional, Brown, Ben James, additional, Bogdanovic, Ozren, additional, Westerfield, Monte, additional, Wardle, Fiona C., additional, Daub, Carsten O., additional, Lenhard, Boris, additional, and Müller, Ferenc, additional
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- 2021
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13. Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop
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Aceto, Nicola, Sausgruber, Nina, Brinkhaus, Heike, Gaidatzis, Dimos, Martiny-Baron, Georg, Mazzarol, Giovanni, Confalonieri, Stefano, Quarto, Micaela, Hu, Guang, Balwierz, Piotr J., Pachkov, Mikhail, Elledge, Stephen J., Nimwegen, Erik van, Stadler, Michael B., and Bentires-Alj, Mohamed
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Phosphatases -- Health aspects -- Physiological aspects -- Genetic aspects -- Research ,Breast cancer -- Development and progression -- Health aspects -- Genetic aspects -- Care and treatment -- Research ,Transcription factors -- Physiological aspects -- Research ,Biological sciences ,Health - Abstract
New cancer therapies are likely to arise from an in-depth understanding of the signaling networks influencing tumor initiation, progression and metastasis. We show a fundamental role for Src-homology 2 domain-containing [...]
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- 2012
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14. Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways
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Gruber, Andreas J., Grandy, William A., Balwierz, Piotr J., Dimitrova, Yoana A., Pachkov, Mikhail, Ciaudo, Constance, Nimwegen, Erik van, and Zavolan, Mihaela
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- 2014
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15. A promoter-level mammalian expression atlas
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Forrest, Alistair R. R., Kawaji, Hideya, Rehli, Michael, Kenneth Baillie, J., de Hoon, Michiel J. L., Haberle, Vanja, Lassmann, Timo, Kulakovskiy, Ivan V., Lizio, Marina, Itoh, Masayoshi, Andersson, Robin, Mungall, Christopher J., Meehan, Terrence F., Schmeier, Sebastian, Bertin, Nicolas, Jørgensen, Mette, Dimont, Emmanuel, Arner, Erik, Schmidl, Christian, Schaefer, Ulf, Medvedeva, Yulia A., Plessy, Charles, Vitezic, Morana, Severin, Jessica, Semple, Colin A., Ishizu, Yuri, Young, Robert S., Francescatto, Margherita, Alam, Intikhab, Albanese, Davide, Altschuler, Gabriel M., Arakawa, Takahiro, Archer, John A. C., Arner, Peter, Babina, Magda, Rennie, Sarah, Balwierz, Piotr J., Beckhouse, Anthony G., Pradhan-Bhatt, Swati, Blake, Judith A., Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Maxwell Burroughs, A., Califano, Andrea, Cannistraci, Carlo V., Carbajo, Daniel, Chen, Yun, Chierici, Marco, Ciani, Yari, Clevers, Hans C., Dalla, Emiliano, Davis, Carrie A., Detmar, Michael, Diehl, Alexander D., Dohi, Taeko, Drabløs, Finn, Edge, Albert S. B., Edinger, Matthias, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Fagiolini, Michela, Fairbairn, Lynsey, Fang, Hai, Farach-Carson, Mary C., Faulkner, Geoffrey J., Favorov, Alexander V., Fisher, Malcolm E., Frith, Martin C., Fujita, Rie, Fukuda, Shiro, Furlanello, Cesare, Furuno, Masaaki, Furusawa, Jun-ichi, Geijtenbeek, Teunis B., Gibson, Andrew P., Gingeras, Thomas, Goldowitz, Daniel, Gough, Julian, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J., Hamaguchi, Masahide, Hara, Mitsuko, Harbers, Matthias, Harshbarger, Jayson, Hasegawa, Akira, Hasegawa, Yuki, Hashimoto, Takehiro, Herlyn, Meenhard, Hitchens, Kelly J., Ho Sui, Shannan J., Hofmann, Oliver M., Hoof, Ilka, Hori, Fumi, Huminiecki, Lukasz, Iida, Kei, Ikawa, Tomokatsu, Jankovic, Boris R., Jia, Hui, Joshi, Anagha, Jurman, Giuseppe, Kaczkowski, Bogumil, Kai, Chieko, Kaida, Kaoru, Kaiho, Ai, Kajiyama, Kazuhiro, Kanamori-Katayama, Mutsumi, Kasianov, Artem S., Kasukawa, Takeya, Katayama, Shintaro, Kato, Sachi, Kawaguchi, Shuji, Kawamoto, Hiroshi, Kawamura, Yuki I., Kawashima, Tsugumi, Kempfle, Judith S., Kenna, Tony J., Kere, Juha, Khachigian, Levon M., Kitamura, Toshio, Peter Klinken, S., Knox, Alan J., Kojima, Miki, Kojima, Soichi, Kondo, Naoto, Koseki, Haruhiko, Koyasu, Shigeo, Krampitz, Sarah, Kubosaki, Atsutaka, Kwon, Andrew T., Laros, Jeroen F. J., Lee, Weonju, Lennartsson, Andreas, Li, Kang, Lilje, Berit, Lipovich, Leonard, Mackay-sim, Alan, Manabe, Ri-ichiroh, Mar, Jessica C., Marchand, Benoit, Mathelier, Anthony, Mejhert, Niklas, Meynert, Alison, Mizuno, Yosuke, de Lima Morais, David A., Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Motakis, Efthymios, Motohashi, Hozumi, Mummery, Christine L., Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nakazato, Kenichi, van Nimwegen, Erik, Ninomiya, Noriko, Nishiyori, Hiromi, Noma, Shohei, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohmiya, Hiroko, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A., Pain, Arnab, Passier, Robert, Patrikakis, Margaret, Persson, Helena, Piazza, Silvano, Prendergast, James G. D., Rackham, Owen J. L., Ramilowski, Jordan A., Rashid, Mamoon, Ravasi, Timothy, Rizzu, Patrizia, Roncador, Marco, Roy, Sugata, Rye, Morten B., Saijyo, Eri, Sajantila, Antti, Saka, Akiko, Sakaguchi, Shimon, Sakai, Mizuho, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schneider, Claudio, Schultes, Erik A., Schulze-Tanzil, Gundula G., Schwegmann, Anita, Sengstag, Thierry, Sheng, Guojun, Shimoji, Hisashi, Shimoni, Yishai, Shin, Jay W., Simon, Christophe, Sugiyama, Daisuke, Sugiyama, Takaaki, Suzuki, Masanori, Suzuki, Naoko, Swoboda, Rolf K., ’t Hoen, Peter A. C., Tagami, Michihira, Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tatum, Zuotian, Thompson, Mark, Toyoda, Hiroo, Toyoda, Tetsuro, Valen, Eivind, van de Wetering, Marc, van den Berg, Linda M., Verardo, Roberto, Vijayan, Dipti, Vorontsov, Ilya E., Wasserman, Wyeth W., Watanabe, Shoko, Wells, Christine A., Winteringham, Louise N., Wolvetang, Ernst, Wood, Emily J., Yamaguchi, Yoko, Yamamoto, Masayuki, Yoneda, Misako, Yonekura, Yohei, Yoshida, Shigehiro, Zabierowski, Susan E., Zhang, Peter G., Zhao, Xiaobei, Zucchelli, Silvia, Summers, Kim M., Suzuki, Harukazu, Daub, Carsten O., Kawai, Jun, Heutink, Peter, Hide, Winston, Freeman, Tom C., Lenhard, Boris, Bajic, Vladimir B., Taylor, Martin S., Makeev, Vsevolod J., Sandelin, Albin, Hume, David A., Carninci, Piero, and Hayashizaki, Yoshihide
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- 2014
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16. Identification of Downstream Effectors of Retinoic Acid Specifying the Zebrafish Pancreas by Integrative Genomics.
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López-Pérez, Ana R., primary, Balwierz, Piotr J., additional, Lenhard, Boris, additional, Muller, Ferenc, additional, Wardle, Fiona C., additional, Manfroid, Isabelle, additional, Voz, Marianne L., additional, and Peers, Bernard, additional
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- 2021
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17. SwissRegulon, a database of genome-wide annotations of regulatory sites: recent updates
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Pachkov, Mikhail, Balwierz, Piotr J., Arnold, Phil, Ozonov, Evgeniy, and van Nimwegen, Erik
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- 2013
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18. Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity
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Arner, Erik, Mejhert, Niklas, Kulyté, Agné, Balwierz, Piotr J., Pachkov, Mikhail, Cormont, Mireille, Lorente-Cebrián, Silvia, Ehrlund, Anna, Laurencikiene, Jurga, Hedén, Per, Dahlman-Wright, Karin, Tanti, Jean-François, Hayashizaki, Yoshihide, Rydén, Mikael, Dahlman, Ingrid, van Nimwegen, Erik, Daub, Carsten O., and Arner, Peter
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- 2012
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19. Identification of downstream effectors of retinoic acid specifying the zebrafish pancreas by integrative genomics
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López-Pérez, Ana R., primary, Balwierz, Piotr J., additional, Lenhard, Boris, additional, Muller, Ferenc, additional, Wardle, Fiona C., additional, Manfroid, Isabelle, additional, Voz, Marianne L., additional, and Peers, Bernard, additional
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- 2020
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20. The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing
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Kishore, Shivendra, Khanna, Amit, Zhang, Zhaiyi, Hui, Jingyi, Balwierz, Piotr J., Stefan, Mihaela, Beach, Carol, Nicholls, Robert D., Zavolan, Mihaela, and Stamm, Stefan
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- 2010
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21. Germ plasm localisation dynamics mark distinct phases of transcriptional and post-transcriptional regulation control in primordial germ cells
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D’Orazio, Fabio M., primary, Balwierz, Piotr, additional, Guo, Yixuan, additional, Hernández-Rodríguez, Benjamín, additional, Jasiulewicz, Aleksandra, additional, Vaquerizas, Juan M., additional, Cairns, Bradley, additional, Lenhard, Boris, additional, and Müller, Ferenc, additional
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- 2020
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22. An epigenetic profile of early T-cell development from multipotent progenitors to committed T-cell descendants
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Vigano, Maria Alessandra, Ivanek, Robert, Balwierz, Piotr, Berninger, Philipp, van Nimwegen, Erik, Karjalainen, Klaus, Rolink, Antonius, and School of Biological Sciences
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Epigenomics ,Mice, Knockout ,Mice, Inbred BALB C ,Precursor Cells, T-Lymphoid ,Lysine ,Multipotent Stem Cells ,T-Lymphocytes ,Cell Differentiation ,Hematopoietic Stem Cells ,Methylation ,Epigenesis, Genetic ,Histones ,Mice, Inbred C57BL ,Mice ,Animals ,Cluster Analysis ,Science::Medicine [DRNTU] ,Cell Lineage ,Cells, Cultured ,Oligonucleotide Array Sequence Analysis - Abstract
Cellular differentiation of the T-cell branch of the immune system begins with the HSC, which undergoes a series of stages characterized by progressive restriction in multipotency and acquisition of specific lineage identity At the molecular level, the restriction of cell potential, commitment, and differentiation to a specific lineage is achieved through the coordinated control of gene expression and epigenetic mechanisms. Here, we analyzed and compared the gene expression profiles and the genome-wide histone modification marks H3K4me3 (H3 lysine 4 trimethylation) and H3K27me3 (H3 lysine 27 trimethylation) in (i) in vitro propagated HSCs, (ii) in vitro generated and propagated pro-T cells derived from these stem cells, and (iii) double-positive thymocytes derived from these pro-T cells after injection into Rag-deficient mice. The combined analyses of the different datasets in this unique experimental system highlighted the importance of both transcriptional and epigenetic repression in shaping the early phases of T-cell development.
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- 2014
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23. Amphioxus functional genomics and the origins of vertebrate gene regulation
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European Research Council, European Commission, Ministerio de Economía y Competitividad (España), Australian Research Council, Marlétaz, Ferdinand, Firbas, Panos, Maeso, Ignacio, Tena, Juan J., Bogdanovic, Ozren, Perry, M., Wyatt, Christopher D. R., Calle-Mustienes, Elisa de la, Bertrand, Stephanie, Burguera, Demian, Acemel, Rafael D., Van Heeringen, Simon J., Naranjo, Silvia, Herrera-Úbeda, Carlos, Skvortsova, Ksenia, Jiménez-Gancedo, Sandra, Aldea, Daniel, Marquez, Yamile, Buono, Lorena, Kozmikova, Iryna, Permanyer, Jon, Louis, Alexandra, Albuixech-Crespo, Beatriz, Petillon, Yann Le, Leon, Anthony, Subirana, Lucie, Balwierz, Piotr J., Duckett, Paul Edward, Farahani, Ensieh, Aury, Jean‐Marc, Mangenot, Sophie, Wincker, Patrick, Albalat, Ricard, Benito-Gutiérrez, Èlia, Cañestro, Cristian, Castro, Filipe, D’Aniello, Salvatore, Ferrier, David E. K., Huang, Shengfeng, Laudet, Vincent, Marais, Gabriel A.B., Pontarotti, Pierre, Schubert, Michael, Seitz, Hervé, Somorjai, Ildiko, Takahashi, Tokiharu, Mirabeau, Olivier, Xu, Anlong, Yu, Jr-Kai, Carninci, Piero, Martínez-Morales, Juan Ramón, Roest Crollius, Hugues, Kozmik, Zbynek, Weirauch, Matthew T., Garcia-Fernàndez, Jordi, Lister, Ryan, Lenhard, Boris, Holland, Peter W. H., Escrivá, Héctor, Gómez-Skarmeta, José Luis, Irimia, Manuel, European Research Council, European Commission, Ministerio de Economía y Competitividad (España), Australian Research Council, Marlétaz, Ferdinand, Firbas, Panos, Maeso, Ignacio, Tena, Juan J., Bogdanovic, Ozren, Perry, M., Wyatt, Christopher D. R., Calle-Mustienes, Elisa de la, Bertrand, Stephanie, Burguera, Demian, Acemel, Rafael D., Van Heeringen, Simon J., Naranjo, Silvia, Herrera-Úbeda, Carlos, Skvortsova, Ksenia, Jiménez-Gancedo, Sandra, Aldea, Daniel, Marquez, Yamile, Buono, Lorena, Kozmikova, Iryna, Permanyer, Jon, Louis, Alexandra, Albuixech-Crespo, Beatriz, Petillon, Yann Le, Leon, Anthony, Subirana, Lucie, Balwierz, Piotr J., Duckett, Paul Edward, Farahani, Ensieh, Aury, Jean‐Marc, Mangenot, Sophie, Wincker, Patrick, Albalat, Ricard, Benito-Gutiérrez, Èlia, Cañestro, Cristian, Castro, Filipe, D’Aniello, Salvatore, Ferrier, David E. K., Huang, Shengfeng, Laudet, Vincent, Marais, Gabriel A.B., Pontarotti, Pierre, Schubert, Michael, Seitz, Hervé, Somorjai, Ildiko, Takahashi, Tokiharu, Mirabeau, Olivier, Xu, Anlong, Yu, Jr-Kai, Carninci, Piero, Martínez-Morales, Juan Ramón, Roest Crollius, Hugues, Kozmik, Zbynek, Weirauch, Matthew T., Garcia-Fernàndez, Jordi, Lister, Ryan, Lenhard, Boris, Holland, Peter W. H., Escrivá, Héctor, Gómez-Skarmeta, José Luis, and Irimia, Manuel
- Abstract
Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that—in vertebrates—over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations.
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- 2018
24. ISMARA: Completely automated inference of gene regulatory networks from high-throughput data
- Author
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Pachkov, Mikhail, primary, Balwierz, Piotr J, additional, Arnold, Phil, additional, Gruber, Andreas J, additional, Zavolan, Mihaela, additional, and van Nimwegen, Erik, additional
- Published
- 2017
- Full Text
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25. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome
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Hurst, Laurence D., Ghanbarian, Avazeh T., Forrest, Alistair R R, Huminiecki, Lukasz, Rehli, Michael, Kenneth Baillie, J., de Hoon, Michiel J L, Haberle, Vanja, Lassmann, Timo, Kulakovskiy, Ivan V., Lizio, Marina, Itoh, Masayoshi, Andersson, Robin, Mungall, Christopher J., Meehan, Terrence F., Schmeier, Sebastian, Bertin, Nicolas, Jørgensen, Mette, Dimont, Emmanuel, Arner, Erik, Schmidl, Christian, Schaefer, Ulf, Medvedeva, Yulia A., Plessy, Charles, Vitezic, Morana, Severin, Jessica, Semple, Colin A., Ishizu, Yuri, Young, Robert S., Francescatto, Margherita, Alam, Intikhab, Albanese, Davide, Altschuler, Gabriel M., Arakawa, Takahiro, Archer, John A C, Arner, Peter, Babina, Magda, Baker, Sarah, Balwierz, Piotr J., Beckhouse, Anthony G., Pradhan, Swati Bhatt, Blake, Judith A., Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Maxwell Burroughs, A., Califano, Andrea, Cannistraci, Carlo V., Carbajo, Daniel, Chen, Yun, Chierici, Marco, Ciani, Yari, Clevers, Hans C., Dalla, Emiliano, Davis, Carrie A., Detmar, Michael, Diehl, Alexander D., Dohi, Taeko, Drabløs, Finn, Edge, Albert S B, Edinger, Matthias, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Fagiolini, Michela, Fairbairn, Lynsey, Fang, Hai, Farach-Carson, Mary C., Faulkner, Geoffrey J., Favorov, Alexander V., Fisher, Malcolm E., Frith, Martin C., Fujita, Rie, Fukuda, Shiro, Furlanello, Cesare, Furuno, Masaaki, Furusawa, Jun ichi, Geijtenbeek, Teunis B., Gibson, Andrew, Gingeras, Thomas, Goldowitz, Daniel, Gough, Julian, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J., Hamaguchi, Masahide, Hara, Mitsuko, Harbers, Matthias, Harshbarger, Jayson, Hasegawa, Akira, Hasegawa, Yuki, Hashimoto, Takehiro, Herlyn, Meenhard, Hitchens, Kelly J., Ho Sui, Shannan J., Hofmann, Oliver M., Hoof, Ilka, Hori, Fumi, Iida, Kei, Ikawa, Tomokatsu, Jankovic, Boris R., Jia, Hui, Joshi, Anagha, Jurman, Giuseppe, Kaczkowski, Bogumil, Kai, Chieko, Kaida, Kaoru, Kaiho, Ai, Kajiyama, Kazuhiro, Kanamori, Mutsumi Katayama, Kasianov, Artem S., Kasukawa, Takeya, Katayama, Shintaro, Kato, Sachi, Kawaguchi, Shuji, Kawamoto, Hiroshi, Kawamura, Yuki I., Kawashima, Tsugumi, Kempfle, Judith S., Kenna, Tony J., Kere, Juha, Khachigian, Levon M., Kitamura, Toshio, Peter Klinken, S., Knox, Alan J., Kojima, Miki, Kojima, Soichi, Kondo, Naoto, Koseki, Haruhiko, Koyasu, Shigeo, Krampitz, Sarah, Kubosaki, Atsutaka, Kwon, Andrew T., Laros, Jeroen F J, Lee, Weonju, Lennartsson, Andreas, Li, Kang, Lilje, Berit, Lipovich, Leonard, Mackay, Alan sim, Manabe, Riichiroh, Mar, Jessica C., Marchand, Benoit, Mathelier, Anthony, Mejhert, Niklas, Meynert, Alison, Mizuno, Yosuke, de Lima Morais, David A., Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Motakis, Efthymios, Motohashi, Hozumi, Mummery, Christine L., Murata, Mitsuyoshi, Nagao, Sayaka Sato, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nakazato, Kenichi, van Nimwegen, Erik, Ninomiya, Noriko, Nishiyori, Hiromi, Noma, Shohei, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohmiya, Hiroko, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada, Mariko Hatakeyama, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A., Pain, Arnab, Passier, Robert, Patrikakis, Margaret, Persson, Helena, Piazza, Silvano, Prendergast, James G D, Rackham, Owen J L, Ramilowski, Jordan A., Rashid, Mamoon, Ravasi, Timothy, Rizzu, Patrizia, Roncador, Marco, Roy, Sugata, Rye, Morten B., Saijyo, Eri, Sajantila, Antti, Saka, Akiko, Sakaguchi, Shimon, Sakai, Mizuho, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schneider, Claudio, Schultes, Erik A., Schulze-Tanzil, Gundula G., Schwegmann, Anita, Sengstag, Thierry, Sheng, Guojun, Shimoji, Hisashi, Shimoni, Yishai, Shin, Jay W., Simon, Christophe, Sugiyama, Daisuke, Sugiyama, Takaaki, Suzuki, Masanori, Suzuki, Naoko, Swoboda, Rolf K., 't Hoen, Peter A C, Tagami, Michihira, Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tatum, Zuotian, Thompson, Mark, Toyoda, Hiroo, Toyoda, Tetsuro, Valen, Eivind, van de Wetering, Marc, van den Berg, Linda M., Verardo, Roberto, Vijayan, Dipti, Vorontsov, Ilya E., Wasserman, Wyeth W., Watanabe, Shoko, Wells, Christine A., Winteringham, Louise N., Wolvetang, Ernst, Wood, Emily J., Yamaguchi, Yoko, Yamamoto, Masayuki, Yoneda, Misako, Yonekura, Yohei, Yoshida, Shigehiro, Zabierowski, Suzan E., Zhang, Peter G., Zhao, Xiaobei, Zucchelli, Silvia, Summers, Kim M., Suzuki, Harukazu, Daub, Carsten O., Kawai, Jun, Heutink, Peter, Hide, Winston, Freeman, Tom C., Lenhard, Boris, Bajic, Vladimir B., Taylor, Martin S., Makeev, Vsevolod J., Sandelin, Albin Gustav, Hume, David A., Carninci, Piero, Hayashizaki, Yoshihide, Hubrecht Institute for Developmental Biology and Stem Cell Research, Barton, Nick H, Amsterdam institute for Infection and Immunity, Infectious diseases, and Experimental Immunology
- Subjects
Male ,Medical and Health Sciences ,Essential ,Models ,Gene expression ,Databases, Genetic ,Biology (General) ,Non-U.S. Gov't ,X-linked recessive inheritance ,X chromosome ,Cells, Cultured ,Regulation of gene expression ,Genetics ,Sex Characteristics ,Dosage compensation ,Tumor ,Cultured ,Genes, Essential ,Genome ,Agricultural and Biological Sciences(all) ,General Neuroscience ,Research Support, Non-U.S. Gov't ,Biological Sciences ,Organ Specificity ,Female ,General Agricultural and Biological Sciences ,Research Article ,Human ,X Chromosome ,Retroelements ,QH301-705.5 ,Neuroscience(all) ,1.1 Normal biological development and functioning ,Cells ,Down-Regulation ,Biology ,Research Support ,General Biochemistry, Genetics and Molecular Biology ,Chromosomes ,Cell Line ,Databases ,Genetic ,Species Specificity ,Underpinning research ,Immunology and Microbiology(all) ,Cell Line, Tumor ,Journal Article ,Animals ,Humans ,Comparative Study ,Gene ,Chromosomes, Human, X ,Autosome ,General Immunology and Microbiology ,Agricultural and Veterinary Sciences ,Models, Genetic ,Biochemistry, Genetics and Molecular Biology(all) ,Genome, Human ,Mammalian ,Human Genome ,Chromosomes, Mammalian ,Genes ,Gene Expression Regulation ,Human genome ,FANTOM consortium ,Developmental Biology - Abstract
X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution., Laurence Hurst, Lukasz Huminiecki, and the FANTOM5 consortium propose a new explanation for the peculiar expression properties of genes on the human X chromosome, based on the premise that very high expression levels cannot be achieved on a haploid-expressed chromosome., Author Summary Genes located on the human X chromosome are not a random mix of genes: they tend to be expressed in relatively few tissues or are specific for a particular set of tissues, e.g., brain regions. Prior attempts to explain this skewed gene content have hypothesized that the X chromosome might be peculiar because it has to balance mutations that are advantageous to one sex but deleterious to the other, or because it has to shut down during the process of sperm manufacture in males. Here we suggest and test a third possible explanation: that genes on the X chromosome are limited in their transcription levels and thus tend to be genes that are lowly or specifically expressed. We consider the suggestion that since these genes can only be expressed from one chromosome, as males only have one X, the ability to express a gene at very high rates is limited owing to potential transcriptional traffic jams. As predicted, we find that human X-located genes have maximal expression rates far below that of genes residing on autosomes. When we look at genes that have moved onto or off the X chromosome during recent evolution, we find the maximal expression is higher when not on the X chromosome. We also find that X-located genes that are relatively highly expressed are not able to increase their expression level further. Our model explains both the enrichment for tissue specificity and the paucity of certain tissues with X-located genes. Genes underrepresented on the X are either expressed in many tissues—such genes tend to have high maximal expression—or are from tissues that require a lot of transcription (e.g., fast secreting tissues like the liver). Just as many of the findings cannot be explained by the two earlier models, neither can the traffic jam model explain all the peculiar features of the genes found on the X chromosome. Indeed, we find evidence of a reproduction-related bias in X-located genes, even after allowing for the traffic jam problem.
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- 2015
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26. The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing
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Kishore, Shivendra, Khanna, Amit, Zhang, Zhaiyi, Hui, Jingyi, Balwierz, Piotr J., Stefan, Mihaela, Beach, Carol, Nicholls, Robert D., Zavolan, Mihaela, Stamm, Stefan, Kishore, Shivendra, Khanna, Amit, Zhang, Zhaiyi, Hui, Jingyi, Balwierz, Piotr J., Stefan, Mihaela, Beach, Carol, Nicholls, Robert D., Zavolan, Mihaela, and Stamm, Stefan
- Abstract
The loss of HBII-52 and related C/D box small nucleolar RNA (snoRNA) expression units have been implicated as a cause for the Prader-Willi syndrome (PWS). We recently found that the C/D box snoRNA HBII-52 changes the alternative splicing of the serotonin receptor 2C pre-mRNA, which is different from the traditional C/D box snoRNA function in non-mRNA methylation. Using bioinformatic predictions and experimental verification, we identified five pre-mRNAs (DPM2, TAF1, RALGPS1, PBRM1 and CRHR1) containing alternative exons that are regulated by MBII-52, the mouse homolog of HBII-52. Analysis of a single member of the MBII-52 cluster of snoRNAs by RNase protection and northern blot analysis shows that the MBII-52 expressing unit generates shorter RNAs that originate from the full-length MBII-52 snoRNA through additional processing steps. These novel RNAs associate with hnRNPs and not with proteins associated with canonical C/D box snoRNAs. Our data indicate that not a traditional C/D box snoRNA MBII-52, but a processed version lacking the snoRNA stem is the predominant MBII-52 RNA missing in PWS. This processed snoRNA functions in alternative splice-site selection. Its substitution could be a therapeutic principle for PWS
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- 2017
27. SwissRegulon, a database of genome-wide annotations of regulatory sites: recent updates
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Pachkov, Mikhail, Balwierz, Piotr J., Arnold, Phil, Ozonov, Evgeniy, van Nimwegen, Erik, Pachkov, Mikhail, Balwierz, Piotr J., Arnold, Phil, Ozonov, Evgeniy, and van Nimwegen, Erik
- Abstract
Identification of genomic regulatory elements is essential for understanding the dynamics of cellular processes. This task has been substantially facilitated by the availability of genome sequences for many species and high-throughput data of transcripts and transcription factor (TF) binding. However, rigorous computational methods are necessary to derive accurate genome-wide annotations of regulatory sites from such data. SwissRegulon (http://swissregulon.unibas.ch) is a database containing genome-wide annotations of regulatory motifs, promoters and TF binding sites (TFBSs) in promoter regions across model organisms. Its binding site predictions were obtained with rigorous Bayesian probabilistic methods that operate on orthologous regions from related genomes, and use explicit evolutionary models to assess the evidence of purifying selection on each site. New in the current version of SwissRegulon is a curated collection of 190 mammalian regulatory motifs associated with ∼340 TFs, and TFBS annotations across a curated set of ∼35 000 promoters in both human and mouse. Predictions of TFBSs for Saccharomyces cerevisiae have also been significantly extended and now cover 158 of yeast's ∼180 TFs. All data are accessible through both an easily navigable genome browser with search functions, and as flat files that can be downloaded for further analysis
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- 2017
28. Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways
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Gruber, Andreas J., Grandy, William A., Balwierz, Piotr J., Dimitrova, Yoana A., Pachkov, Mikhail, Ciaudo, Constance, Nimwegen, Erik van, Zavolan, Mihaela, Gruber, Andreas J., Grandy, William A., Balwierz, Piotr J., Dimitrova, Yoana A., Pachkov, Mikhail, Ciaudo, Constance, Nimwegen, Erik van, and Zavolan, Mihaela
- Abstract
The findings that microRNAs (miRNAs) are essential for early development in many species and that embryonic miRNAs can reprogram somatic cells into induced pluripotent stem cells suggest that these miRNAs act directly on transcriptional and chromatin regulators of pluripotency. To elucidate the transcription regulatory networks immediately downstream of embryonic miRNAs, we extended the motif activity response analysis approach that infers the regulatory impact of both transcription factors (TFs) and miRNAs from genome-wide expression states. Applying this approach to multiple experimental data sets generated from mouse embryonic stem cells (ESCs) that did or did not express miRNAs of the ESC-specific miR-290-295 cluster, we identified multiple TFs that are direct miRNA targets, some of which are known to be active during cell differentiation. Our results provide new insights into the transcription regulatory network downstream of ESC-specific miRNAs, indicating that these miRNAs act on cell cycle and chromatin regulators at several levels and downregulate TFs that are involved in the innate immune response
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- 2017
29. Inference of gene regulatory interactions from deep sequencing data
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Balwierz, Piotr J., Nimwegen, Erik van, and Schübeler, Dirk
- Abstract
This thesis describes our work on the inference of gene regulatory interactions from deep sequencing data. In the first part we start with an introduction to the problem of inferring transcription regulatory interactions (Chapter 2). Then we describe detailed methods of promoterome construction in human and mouse genomes from deep CAGE data (Chapter 3), and show how promoters together with gene expression data can be used to infer transcription regulatory interactions (Chapter 4). Finally, we show an application of this methodology to a human macrophage lineage undergoing differentiation accompanied by a detailed experimental validation of the predicted network structure (Chapter 5). Work presented in Chapter 5 comes from the FANTOM4 project. In the second part we focus on the regulatory functions of two small nucleolar RNAs (snoRNAs). In Chapter 8 we describe an atypical function of snoRNAs - regulation of the mRNA alternative splicing process by a particular class of mouse snoRNAs (MBII-52 variants). These are of great interest, as the locus encoding MBII-52 is linked to Prader-Willi Syndrome. Methods include in silico RNA hybridization screens and experimental confirmation of the predictions. In Chapter 9, we report a discovery of the first virus-encoded snoRNA in Epstein-Barr Virus (EBV). Again, we show that the function of this snoRNA (v-snoRNA1) is atypical: it is processed into small, 24 nt long fragments that can function as microRNAs.
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- 2012
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30. A promoter-level mammalian expression atlas
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Forrest, Alistair R R, Kawaji, Hideya, Rehli, Michael, Baillie, J Kenneth, de Hoon, Michiel J L, Haberle, Vanja, Lassman, Timo, Kulakovskiy, Ivan V, Lizio, Marina, Itoh, Masayoshi, Andersson, Robin, Mungall, Christopher J, Meehan, Terrence F, Schmeier, Sebastian, Bertin, Nicolas, Jørgensen, Mette, Dimont, Emmanuel, Arner, Erik, Schmidl, Christian, Schaefer, Ulf, Medvedeva, Yulia A, Plessy, Charles, Vitezic, Morana, Severin, Jessica, Semple, Colin A, Ishizu, Yuri, Young, Robert S, Francescatto, Margherita, Alam, Intikhab, Albanese, Davide, Altschuler, Gabriel M, Arakawa, Takahiro, Archer, John A C, Arner, Peter, Babina, Magda, Rennie, Sarah, Balwierz, Piotr J, Beckhouse, Anthony G, Pradhan-Bhatt, Swati, Blake, Judith A, Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Burroughs, A Maxwell, Califano, Andrea, Cannistraci, Carlo V, Clevers, Hans C, Mummery, Christine L, FANTOM Consortium and the RIKEN PMI and CLST (DGT), Forrest, Alistair R R, Kawaji, Hideya, Rehli, Michael, Baillie, J Kenneth, de Hoon, Michiel J L, Haberle, Vanja, Lassman, Timo, Kulakovskiy, Ivan V, Lizio, Marina, Itoh, Masayoshi, Andersson, Robin, Mungall, Christopher J, Meehan, Terrence F, Schmeier, Sebastian, Bertin, Nicolas, Jørgensen, Mette, Dimont, Emmanuel, Arner, Erik, Schmidl, Christian, Schaefer, Ulf, Medvedeva, Yulia A, Plessy, Charles, Vitezic, Morana, Severin, Jessica, Semple, Colin A, Ishizu, Yuri, Young, Robert S, Francescatto, Margherita, Alam, Intikhab, Albanese, Davide, Altschuler, Gabriel M, Arakawa, Takahiro, Archer, John A C, Arner, Peter, Babina, Magda, Rennie, Sarah, Balwierz, Piotr J, Beckhouse, Anthony G, Pradhan-Bhatt, Swati, Blake, Judith A, Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Burroughs, A Maxwell, Califano, Andrea, Cannistraci, Carlo V, Clevers, Hans C, Mummery, Christine L, and FANTOM Consortium and the RIKEN PMI and CLST (DGT)
- Abstract
Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.
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- 2014
31. A promoter-level mammalian expression atlas
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Forest, Alistair R.R., Kawaji, Hideya, Rehli, Michael, Baillie, J. Kenneth, De Hoon, Michiel J.L., Haberle, Vanja, Lassmann, Timo, Kulakovskiy, Ivan V., Lizio, Marina, Itoh, Masayoshi, Andersson, Robin, Mungall, Christopher J., Meehan, Terrence F., Schmeier, Sebastian, Bertin, Nicolas, Jørgensen, Mette, Dimont, Emmanuel, Arner, Erik, Schmidl, Christian, Schaefer, Ulf, Medvedeva, Yulia A., Plessy, Charles, Vitezic, Morana, Severin, Jessica, Semple, Colin A., Ishizu, Yuri, Young, Robert S., Francescatto, Margherita, Altschuler, Intikhab Alam, Albanese, Davide, Altschule, Gabriel M., Arakawa, Takahiro, Archer, John A C, Arner, Peter, Babina, Magda, Rennie, Sarah, Balwierz, Piotr J., Beckhouse, Anthony G., Pradhan-Bhatt, Swati, Blake, Judith A., Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Burroughs, A. Maxwell, Califano, Andrea, Cannistraci, Carlo V., Carbajo, Daniel, Chen, Yun, Chierici, Marco, Ciani, Yari, Clevers, Hans C., Dalla, Emiliano, Davis, Carrie A., Detmar, Michael, Diehl, Alexander D., Dohi, Taeko, Drabløs, Finn, Edge, Albert S B, Edinger, Matthias, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Fagiolini, Michela, Fairbairn, Lynsey, Fang, Hai, Farach-Carson, Mary C., Faulkner, Geoffrey J., Favorov, Alexander V., Fisher, Malcolm E., Frith, Martin C., Fujita, Rie, Fukuda, Shiro, Furlanello, Cesare, Furuno, Masaaki, Furusawa, Jun Ichi, Geijtenbeek, Teunis B., Gibson, Andrew P., Gingeras, Thomas, Goldowitz, Daniel, Gough, Julian, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J., Hamaguchi, Masahide, Hara, Mitsuko, Harbers, Matthias, Harshbarger, Jayson, Hasegawa, Akira, Hasegawa, Yuki, Hashimoto, Takehiro, Herlyn, Meenhard, Hitchens, Kelly J., Sui, Shannan J Ho, Hofmann, Oliver M., Hoof, Ilka, Hori, Fumi, Huminiecki, Lukasz, Iida, Kei, Ikawa, Tomokatsu, Jankovic, Boris R., Jia, Hui, Joshi, Anagha, Jurman, Giuseppe, Kaczkowski, Bogumil, Kai, Chieko, Kaida, Kaoru, Kaiho, Ai, Kajiyama, Kazuhiro, Kanamori-Katayama, Mutsumi, Kasianov, Artem S., Kasukawa, Takeya, Katayama, Shintaro, Kato, Sachi, Kawaguchi, Shuji, Kawamoto, Hiroshi, Kawamura, Yuki I., Kawashima, Tsugumi, Kempfle, Judith S., Kenna, Tony J., Kere, Juha, Khachigian, Levon M., Kitamura, Toshio, Klinken, S. Peter, Knox, Alan J., Kojima, Miki, Kojima, Soichi, Kondo, Naoto, Koseki, Haruhiko, Koyasu, Shigeo, Krampitz, Sarah, Kubosaki, Atsutaka, Kwon, Andrew T., Laros, Jeroen F J, Lee, Weonju, Lennartsson, Andreas, Li, Kang, Lilje, Berit, Lipovich, Leonard, Mackay-sim, Alan, Manabe, Ri Ichiroh, Mar, Jessica C., Marchand, Benoit, Mathelier, Anthony, Mejhert, Niklas, Meynert, Alison, Mizuno, Yosuke, De Morais, David A Lima, Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Motakis, Efthymios, Motohashi, Hozumi, Mummery, Christine L., Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nakazato, Kenichi, Van Nimwegen, Erik, Ninomiya, Noriko, Nishiyori, Hiromi, Noma, Shohei, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohmiya, Hiroko, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A., Pain, Arnab, Passier, Robert, Patrikakis, Margaret, Persson, Helena, Piazza, Silvano, Prendergast, James G D, Rackham, Owen J L, Ramilowski, Jordan A., Rashid, Mamoon, Ravasi, Timothy, Rizzu, Patrizia, Roncador, Marco, Roy, Sugata, Rye, Morten B., Saijyo, Eri, Sajantila, Antti, Saka, Akiko, Sakaguchi, Shimon, Sakai, Mizuho, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schneider, Claudio, Schultes, Erik A., Schulze-Tanzil, Gundula G., Schwegmann, Anita, Sengstag, Thierry, Sheng, Guojun, Shimoji, Hisashi, Shimoni, Yishai, Shin, Jay W., Simon, Christophe, Sugiyama, Daisuke, Sugiyama, Takaaki, Suzuki, Masanori, Suzuki, Naoko, Swoboda, Rolf K., 'T Hoen, Peter A C, Tagami, Michihira, Tagami, Naoko Takahashi, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tatum, Zuotian, Thompson, Mark, Toyoda, Hiroo, Toyoda, Tetsuro, Valen, Eivind, Van De Wetering, Marc, Van Den Berg, Linda M., Verardo, Roberto, Vijayan, Dipti, Vorontsov, Ilya E., Wasserman, Wyeth W., Watanabe, Shoko, Wells, Christine A., Winteringham, Louise N., Wolvetang, Ernst, Wood, Emily J., Yamaguchi, Yoko, Yamamoto, Masayuki, Yoneda, Misako, Yonekura, Yohei, Yoshida, Shigehiro, Zabierowski, Susan E., Zhang, Peter G., Zhao, Xiaobei, Zucchelli, Silvia, Summers, Kim M., Suzuki, Harukazu, Daub, Carsten O., Kawai, Jun, Heutink, Peter, Hide, Winston, Freeman, Tom C., Lenhard, Boris, Bajic, Lenhard Vladimir B, Taylor, Martin S., Makeev, Vsevolod J., Sandelin, Albin Gustav, Hume, David A., Carninci, Piero, Hayashizaki, Yoshihide, Forest, Alistair R.R., Kawaji, Hideya, Rehli, Michael, Baillie, J. Kenneth, De Hoon, Michiel J.L., Haberle, Vanja, Lassmann, Timo, Kulakovskiy, Ivan V., Lizio, Marina, Itoh, Masayoshi, Andersson, Robin, Mungall, Christopher J., Meehan, Terrence F., Schmeier, Sebastian, Bertin, Nicolas, Jørgensen, Mette, Dimont, Emmanuel, Arner, Erik, Schmidl, Christian, Schaefer, Ulf, Medvedeva, Yulia A., Plessy, Charles, Vitezic, Morana, Severin, Jessica, Semple, Colin A., Ishizu, Yuri, Young, Robert S., Francescatto, Margherita, Altschuler, Intikhab Alam, Albanese, Davide, Altschule, Gabriel M., Arakawa, Takahiro, Archer, John A C, Arner, Peter, Babina, Magda, Rennie, Sarah, Balwierz, Piotr J., Beckhouse, Anthony G., Pradhan-Bhatt, Swati, Blake, Judith A., Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Burroughs, A. Maxwell, Califano, Andrea, Cannistraci, Carlo V., Carbajo, Daniel, Chen, Yun, Chierici, Marco, Ciani, Yari, Clevers, Hans C., Dalla, Emiliano, Davis, Carrie A., Detmar, Michael, Diehl, Alexander D., Dohi, Taeko, Drabløs, Finn, Edge, Albert S B, Edinger, Matthias, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Fagiolini, Michela, Fairbairn, Lynsey, Fang, Hai, Farach-Carson, Mary C., Faulkner, Geoffrey J., Favorov, Alexander V., Fisher, Malcolm E., Frith, Martin C., Fujita, Rie, Fukuda, Shiro, Furlanello, Cesare, Furuno, Masaaki, Furusawa, Jun Ichi, Geijtenbeek, Teunis B., Gibson, Andrew P., Gingeras, Thomas, Goldowitz, Daniel, Gough, Julian, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J., Hamaguchi, Masahide, Hara, Mitsuko, Harbers, Matthias, Harshbarger, Jayson, Hasegawa, Akira, Hasegawa, Yuki, Hashimoto, Takehiro, Herlyn, Meenhard, Hitchens, Kelly J., Sui, Shannan J Ho, Hofmann, Oliver M., Hoof, Ilka, Hori, Fumi, Huminiecki, Lukasz, Iida, Kei, Ikawa, Tomokatsu, Jankovic, Boris R., Jia, Hui, Joshi, Anagha, Jurman, Giuseppe, Kaczkowski, Bogumil, Kai, Chieko, Kaida, Kaoru, Kaiho, Ai, Kajiyama, Kazuhiro, Kanamori-Katayama, Mutsumi, Kasianov, Artem S., Kasukawa, Takeya, Katayama, Shintaro, Kato, Sachi, Kawaguchi, Shuji, Kawamoto, Hiroshi, Kawamura, Yuki I., Kawashima, Tsugumi, Kempfle, Judith S., Kenna, Tony J., Kere, Juha, Khachigian, Levon M., Kitamura, Toshio, Klinken, S. Peter, Knox, Alan J., Kojima, Miki, Kojima, Soichi, Kondo, Naoto, Koseki, Haruhiko, Koyasu, Shigeo, Krampitz, Sarah, Kubosaki, Atsutaka, Kwon, Andrew T., Laros, Jeroen F J, Lee, Weonju, Lennartsson, Andreas, Li, Kang, Lilje, Berit, Lipovich, Leonard, Mackay-sim, Alan, Manabe, Ri Ichiroh, Mar, Jessica C., Marchand, Benoit, Mathelier, Anthony, Mejhert, Niklas, Meynert, Alison, Mizuno, Yosuke, De Morais, David A Lima, Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Motakis, Efthymios, Motohashi, Hozumi, Mummery, Christine L., Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nakazato, Kenichi, Van Nimwegen, Erik, Ninomiya, Noriko, Nishiyori, Hiromi, Noma, Shohei, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohmiya, Hiroko, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A., Pain, Arnab, Passier, Robert, Patrikakis, Margaret, Persson, Helena, Piazza, Silvano, Prendergast, James G D, Rackham, Owen J L, Ramilowski, Jordan A., Rashid, Mamoon, Ravasi, Timothy, Rizzu, Patrizia, Roncador, Marco, Roy, Sugata, Rye, Morten B., Saijyo, Eri, Sajantila, Antti, Saka, Akiko, Sakaguchi, Shimon, Sakai, Mizuho, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schneider, Claudio, Schultes, Erik A., Schulze-Tanzil, Gundula G., Schwegmann, Anita, Sengstag, Thierry, Sheng, Guojun, Shimoji, Hisashi, Shimoni, Yishai, Shin, Jay W., Simon, Christophe, Sugiyama, Daisuke, Sugiyama, Takaaki, Suzuki, Masanori, Suzuki, Naoko, Swoboda, Rolf K., 'T Hoen, Peter A C, Tagami, Michihira, Tagami, Naoko Takahashi, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tatum, Zuotian, Thompson, Mark, Toyoda, Hiroo, Toyoda, Tetsuro, Valen, Eivind, Van De Wetering, Marc, Van Den Berg, Linda M., Verardo, Roberto, Vijayan, Dipti, Vorontsov, Ilya E., Wasserman, Wyeth W., Watanabe, Shoko, Wells, Christine A., Winteringham, Louise N., Wolvetang, Ernst, Wood, Emily J., Yamaguchi, Yoko, Yamamoto, Masayuki, Yoneda, Misako, Yonekura, Yohei, Yoshida, Shigehiro, Zabierowski, Susan E., Zhang, Peter G., Zhao, Xiaobei, Zucchelli, Silvia, Summers, Kim M., Suzuki, Harukazu, Daub, Carsten O., Kawai, Jun, Heutink, Peter, Hide, Winston, Freeman, Tom C., Lenhard, Boris, Bajic, Lenhard Vladimir B, Taylor, Martin S., Makeev, Vsevolod J., Sandelin, Albin Gustav, Hume, David A., Carninci, Piero, and Hayashizaki, Yoshihide
- Abstract
Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly â ̃ housekeepingâ ™, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.
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- 2014
32. ISMARA: automated modeling of genomic signals as a democracy of regulatory motifs
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Balwierz, Piotr J., primary, Pachkov, Mikhail, additional, Arnold, Phil, additional, Gruber, Andreas J., additional, Zavolan, Mihaela, additional, and van Nimwegen, Erik, additional
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- 2014
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33. Modeling of epigenome dynamics identifies transcription factors that mediate Polycomb targeting
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Arnold, Phil, Schöler, Anne, Pachkov, Mikhail, Balwierz, Piotr J, Jørgensen, Helle, Stadler, Michael B, van Nimwegen, Erik, Schübeler, Dirk, Arnold, Phil, Schöler, Anne, Pachkov, Mikhail, Balwierz, Piotr J, Jørgensen, Helle, Stadler, Michael B, van Nimwegen, Erik, and Schübeler, Dirk
- Abstract
Although changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. To systematically identify transcription factors (TFs) that can direct chromatin changes during cell fate decisions, we model the relationship between genome-wide dynamics of chromatin marks and the local occurrence of computationally predicted TF binding sites. By applying this computational approach to a time course of Polycomb-mediated H3K27me3 marks during neuronal differentiation of murine stem cells, we identify several motifs that likely regulate the dynamics of this chromatin mark. Among these, the sites bound by REST and by the SNAIL family of TFs are predicted to transiently recruit H3K27me3 in neuronal progenitors. We validate these predictions experimentally and show that absence of REST indeed causes loss of H3K27me3 at target promoters in trans, specifically at the neuronal progenitor state. Moreover, using targeted transgenic insertion, we show that promoter fragments containing REST or SNAIL binding sites are sufficient to recruit H3K27me3 in cis, while deletion of these sites results in loss of H3K27me3. These findings illustrate that the occurrence of TF binding sites can determine chromatin dynamics. Local determination of Polycomb activity by REST and SNAIL motifs exemplifies such TF based regulation of chromatin. Furthermore, our results show that key TFs can be identified ab initio through computational modeling of epigenome data sets using a modeling approach that we make readily accessible
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- 2013
34. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line
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Suzuki, Harukazu, Forrest, Alistair R R, van Nimwegen, Erik, Daub, Carsten O, Balwierz, Piotr J, Irvine, Katharine M, Lassmann, Timo, Ravasi, Timothy, Hasegawa, Yuki, de Hoon, Michiel J L, Katayama, Shintaro, Schroder, Kate, Carninci, Piero, Tomaru, Yasuhiro, Kanamori-Katayama, Mutsumi, Kubosaki, Atsutaka, Akalin, Altuna, Ando, Yoshinari, Arner, Erik, Asada, Maki, Asahara, Hiroshi, Bailey, Timothy, Bajic, Vladimir B, Bauer, Denis, Beckhouse, Anthony G, Bertin, Nicolas, Björkegren, Johan, Brombacher, Frank, Bulger, Erika, Chalk, Alistair M, Chiba, Joe, Cloonan, Nicole, Dawe, Adam, Dostie, Josee, Engström, Pär G, Essack, Magbubah, Faulkner, Geoffrey J, Fink, J Lynn, Fredman, David, Fujimori, Ko, Furuno, Masaaki, Gojobori, Takashi, Gough, Julian, Grimmond, Sean M, Jacobsen, Anders, Krogh, Anders, Nygaard, Sanne, Sandelin, Albin, Valen, Eivind, Winther, Ole, Suzuki, Harukazu, Forrest, Alistair R R, van Nimwegen, Erik, Daub, Carsten O, Balwierz, Piotr J, Irvine, Katharine M, Lassmann, Timo, Ravasi, Timothy, Hasegawa, Yuki, de Hoon, Michiel J L, Katayama, Shintaro, Schroder, Kate, Carninci, Piero, Tomaru, Yasuhiro, Kanamori-Katayama, Mutsumi, Kubosaki, Atsutaka, Akalin, Altuna, Ando, Yoshinari, Arner, Erik, Asada, Maki, Asahara, Hiroshi, Bailey, Timothy, Bajic, Vladimir B, Bauer, Denis, Beckhouse, Anthony G, Bertin, Nicolas, Björkegren, Johan, Brombacher, Frank, Bulger, Erika, Chalk, Alistair M, Chiba, Joe, Cloonan, Nicole, Dawe, Adam, Dostie, Josee, Engström, Pär G, Essack, Magbubah, Faulkner, Geoffrey J, Fink, J Lynn, Fredman, David, Fujimori, Ko, Furuno, Masaaki, Gojobori, Takashi, Gough, Julian, Grimmond, Sean M, Jacobsen, Anders, Krogh, Anders, Nygaard, Sanne, Sandelin, Albin, Valen, Eivind, and Winther, Ole
- Abstract
Udgivelsesdato: 2009-May, Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.
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- 2009
35. The Corepressor NCoR1 Antagonizes PGC-1α and Estrogen-Related Receptor α in the Regulation of Skeletal Muscle Function and Oxidative Metabolism
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Pérez-Schindler, Joaquín, primary, Summermatter, Serge, additional, Salatino, Silvia, additional, Zorzato, Francesco, additional, Beer, Markus, additional, Balwierz, Piotr J., additional, van Nimwegen, Erik, additional, Feige, Jérôme N., additional, Auwerx, Johan, additional, and Handschin, Christoph, additional
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- 2012
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36. SwissRegulon, a database of genome-wide annotations of regulatory sites: recent updates
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Pachkov, Mikhail, primary, Balwierz, Piotr J., additional, Arnold, Phil, additional, Ozonov, Evgeniy, additional, and van Nimwegen, Erik, additional
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- 2012
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- View/download PDF
37. Modeling of epigenome dynamics identifies transcription factors that mediate Polycomb targeting
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Arnold, Phil, primary, Schöler, Anne, additional, Pachkov, Mikhail, additional, Balwierz, Piotr J., additional, Jørgensen, Helle, additional, Stadler, Michael B., additional, van Nimwegen, Erik, additional, and Schübeler, Dirk, additional
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- 2012
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38. Long-term effects of early pregnancy on the gene expression and properties of mammary epithelial cell subpopulations in mice
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Meier-Abt Fabienne, Milani Emanuela, Roloff Tim, Brinkhaus Heike, Duss Stephan, Meyer Dominique S, Klebba Ina, Balwierz Piotr J, van Nimwegen Erik, and Bentires-Alj Mohamed
- Abstract
The breast cancer protective effect of an early pregnancy is well established in humans and rodents but the underlying mechanism is unclear. Since breast cancers are thought to originate from specific cell subpopulations of mammary epithelia we studied the effect of early parity on the gene expression and properties of specific luminal and basal mammary cells in mice. Thereby mammary epithelial cell subpopulations were isolated by flow cytometry from parous and age matched nulliparous mice and investigated using unbiased genomics and bioinformatics as well as in vitro colony formation and in vivo mammary gland reconstitution assays. The results of the transcriptome analysis showed an upregulation of differentiation genes and a pronounced decrease in the Wnt/Notch signaling ratio in basal stem/progenitor cells. This was associated with a downregulation of carcinogenic pathways and a strong reduction in the proliferation potential of this cell subpopulation in vitro and to a lesser extent in vivo indicating that basal stem/progenitor cells are the main target of pregnancy. As a possible mechanism for reduced Wnt signaling in basal stem/progenitor cells we found a 2 fold decrease in the expression of the secreted Wnt ligand Wnt4 in mammary cells from parous mice. This corresponded to a similar decrease in the progesterone receptor positive and Wnt4 secreting cells. Notably Wnt4 partially rescued the in vitro proliferation failure of basal stem/progenitor cells strongly suggesting a causal relationship between decreased Wnt4 secretion and parity induced changes in the gene expression and properties of basal stem/progenitor cells in mice. In conclusion our study shows that early parity induces differentiation and downregulates the Wnt/Notch signaling ratio and the in vitro and in vivo proliferation potential of basal stem/progenitor cells in mice. Thereby our study not only delineates the long term effects of early parity but it also paves the way for future studies examining whether inhibitors of Wnt signaling can be used to mimic the parity induced protective effect against breast cancer.
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- 2013
39. Expression and Processing of a Small Nucleolar RNA from the Epstein-Barr Virus Genome
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Hutzinger, Roland, primary, Feederle, Regina, additional, Mrazek, Jan, additional, Schiefermeier, Natalia, additional, Balwierz, Piotr J., additional, Zavolan, Mihaela, additional, Polacek, Norbert, additional, Delecluse, Henri-Jacques, additional, and Hüttenhofer, Alexander, additional
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- 2009
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40. FANTOM4 EdgeExpressDB: an integrated database of promoters, genes, microRNAs, expression dynamics and regulatory interactions
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Severin, Jessica, primary, Waterhouse, Andrew M, additional, Kawaji, Hideya, additional, Lassmann, Timo, additional, van Nimwegen, Erik, additional, Balwierz, Piotr J, additional, de Hoon, Michiel JL, additional, Hume, David A, additional, Carninci, Piero, additional, Hayashizaki, Yoshihide, additional, Suzuki, Harukazu, additional, Daub, Carsten O, additional, and Forrest, Alistair RR, additional
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- 2009
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41. Methods for analyzing deep sequencing expression data: constructing the human and mouse promoterome with deepCAGE data
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Balwierz, Piotr J, primary, Carninci, Piero, additional, Daub, Carsten O, additional, Kawai, Jun, additional, Hayashizaki, Yoshihide, additional, Van Belle, Werner, additional, Beisel, Christian, additional, and van Nimwegen, Erik, additional
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- 2009
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42. Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways
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Gruber, Andreas J., Grandy, William A., Balwierz, Piotr J., Dimitrova, Yoana A., Pachkov, Mikhail, Ciaudo, Constance, van Nimwegen, Erik, and Zavolan, Mihaela
- Subjects
3. Good health - Abstract
The findings that microRNAs (miRNAs) are essential for early development in many species and that embryonic miRNAs can reprogram somatic cells into induced pluripotent stem cells suggest that these miRNAs act directly on transcriptional and chromatin regulators of pluripotency. To elucidate the transcription regulatory networks immediately downstream of embryonic miRNAs, we extended the motif activity response analysis approach that infers the regulatory impact of both transcription factors (TFs) and miRNAs from genome-wide expression states. Applying this approach to multiple experimental data sets generated from mouse embryonic stem cells (ESCs) that did or did not express miRNAs of the ESC-specific miR-290-295 cluster, we identified multiple TFs that are direct miRNA targets, some of which are known to be active during cell differentiation. Our results provide new insights into the transcription regulatory network downstream of ESC-specific miRNAs, indicating that these miRNAs act on cell cycle and chromatin regulators at several levels and downregulate TFs that are involved in the innate immune response., Nucleic Acids Research, 42 (14), ISSN:1362-4962, ISSN:0301-5610
43. Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways
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Gruber, Andreas J., Grandy, William A., Balwierz, Piotr J., Dimitrova, Yoana A., Pachkov, Mikhail, Ciaudo, Constance, van Nimwegen, Erik, and Zavolan, Mihaela
- Subjects
3. Good health
44. The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing
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Kishore, Shivendra, Khanna, Amit, Zhang, Zhaiyi, Hui, Jingyi, Balwierz, Piotr J., Stefan, Mihaela, Beach, Carol, Nicholls, Robert D., Zavolan, Mihaela, Stamm, Stefan, Kishore, Shivendra, Khanna, Amit, Zhang, Zhaiyi, Hui, Jingyi, Balwierz, Piotr J., Stefan, Mihaela, Beach, Carol, Nicholls, Robert D., Zavolan, Mihaela, and Stamm, Stefan
- Abstract
The loss of HBII-52 and related C/D box small nucleolar RNA (snoRNA) expression units have been implicated as a cause for the Prader-Willi syndrome (PWS). We recently found that the C/D box snoRNA HBII-52 changes the alternative splicing of the serotonin receptor 2C pre-mRNA, which is different from the traditional C/D box snoRNA function in non-mRNA methylation. Using bioinformatic predictions and experimental verification, we identified five pre-mRNAs (DPM2, TAF1, RALGPS1, PBRM1 and CRHR1) containing alternative exons that are regulated by MBII-52, the mouse homolog of HBII-52. Analysis of a single member of the MBII-52 cluster of snoRNAs by RNase protection and northern blot analysis shows that the MBII-52 expressing unit generates shorter RNAs that originate from the full-length MBII-52 snoRNA through additional processing steps. These novel RNAs associate with hnRNPs and not with proteins associated with canonical C/D box snoRNAs. Our data indicate that not a traditional C/D box snoRNA MBII-52, but a processed version lacking the snoRNA stem is the predominant MBII-52 RNA missing in PWS. This processed snoRNA functions in alternative splice-site selection. Its substitution could be a therapeutic principle for PWS
45. SwissRegulon, a database of genome-wide annotations of regulatory sites: recent updates
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Pachkov, Mikhail, Balwierz, Piotr J., Arnold, Phil, Ozonov, Evgeniy, van Nimwegen, Erik, Pachkov, Mikhail, Balwierz, Piotr J., Arnold, Phil, Ozonov, Evgeniy, and van Nimwegen, Erik
- Abstract
Identification of genomic regulatory elements is essential for understanding the dynamics of cellular processes. This task has been substantially facilitated by the availability of genome sequences for many species and high-throughput data of transcripts and transcription factor (TF) binding. However, rigorous computational methods are necessary to derive accurate genome-wide annotations of regulatory sites from such data. SwissRegulon (http://swissregulon.unibas.ch) is a database containing genome-wide annotations of regulatory motifs, promoters and TF binding sites (TFBSs) in promoter regions across model organisms. Its binding site predictions were obtained with rigorous Bayesian probabilistic methods that operate on orthologous regions from related genomes, and use explicit evolutionary models to assess the evidence of purifying selection on each site. New in the current version of SwissRegulon is a curated collection of 190 mammalian regulatory motifs associated with ∼340 TFs, and TFBS annotations across a curated set of ∼35 000 promoters in both human and mouse. Predictions of TFBSs for Saccharomyces cerevisiae have also been significantly extended and now cover 158 of yeast's ∼180 TFs. All data are accessible through both an easily navigable genome browser with search functions, and as flat files that can be downloaded for further analysis
46. Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways
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Gruber, Andreas J., Grandy, William A., Balwierz, Piotr J., Dimitrova, Yoana A., Pachkov, Mikhail, Ciaudo, Constance, Nimwegen, Erik van, Zavolan, Mihaela, Gruber, Andreas J., Grandy, William A., Balwierz, Piotr J., Dimitrova, Yoana A., Pachkov, Mikhail, Ciaudo, Constance, Nimwegen, Erik van, and Zavolan, Mihaela
- Abstract
The findings that microRNAs (miRNAs) are essential for early development in many species and that embryonic miRNAs can reprogram somatic cells into induced pluripotent stem cells suggest that these miRNAs act directly on transcriptional and chromatin regulators of pluripotency. To elucidate the transcription regulatory networks immediately downstream of embryonic miRNAs, we extended the motif activity response analysis approach that infers the regulatory impact of both transcription factors (TFs) and miRNAs from genome-wide expression states. Applying this approach to multiple experimental data sets generated from mouse embryonic stem cells (ESCs) that did or did not express miRNAs of the ESC-specific miR-290-295 cluster, we identified multiple TFs that are direct miRNA targets, some of which are known to be active during cell differentiation. Our results provide new insights into the transcription regulatory network downstream of ESC-specific miRNAs, indicating that these miRNAs act on cell cycle and chromatin regulators at several levels and downregulate TFs that are involved in the innate immune response
47. Amphioxus functional genomics and the origins of vertebrate gene regulation
- Author
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Patrick Wincker, Pierre Pontarotti, Elisa de la Calle-Mustienes, Zbynek Kozmik, Malcolm Perry, José Luis Gómez-Skarmeta, Cristian Cañestro, Stéphanie Bertrand, Yamile Marquez, Èlia Benito-Gutiérrez, Juan J. Tena, Hector Escriva, Alexandra Louis, Anthony Leon, Matthew T. Weirauch, Juan Ramón Martínez-Morales, Panos N. Firbas, Peter W. H. Holland, Iryna Kozmikova, Daniel Aldea, Sandra Jiménez-Gancedo, Jordi Garcia-Fernàndez, Jean-Marc Aury, Michael Schubert, Paul Edward Duckett, Beatriz Albuixech-Crespo, Simon J. van Heeringen, Boris Lenhard, Piero Carninci, Carlos Herrera-Úbeda, Olivier Mirabeau, Demian Burguera, Lorena Buono, Tokiharu Takahashi, Rafael D. Acemel, Silvia Naranjo, Ryan Lister, Sophie Mangenot, Lucie Subirana, Ksenia Skvortsova, Jr-Kai Yu, Hugues Roest Crollius, Ildiko M. L. Somorjai, Vincent Laudet, Piotr J. Balwierz, Gabriel A. B. Marais, Ignacio Maeso, Anlong Xu, Christopher D. R. Wyatt, Shengfeng Huang, Ozren Bogdanovic, David E. K. Ferrier, Ferdinand Marlétaz, Salvatore D'Aniello, Jon Permanyer, Filipe Castro, Manuel Irimia, Ricard Albalat, Yann Le Petillon, Ensieh Farahani, Hervé Seitz, Okinawa Institute of Science and Technology Graduate University (OIST), Department of Zoology [Oxford], University of Oxford, Centro Andaluz de Biología del Desarrollo, Universidad Pablo Olavide, University of New South Wales [Sydney] (UNSW), The University of Western Australia (UWA), Imperial College London, Universitat Pompeu Fabra [Barcelona] (UPF), Biologie intégrative des organismes marins (BIOM), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Barcelona Institute of Science and Technology (BIST), Universidad Pablo de Olavide [Sevilla] (UPO), Radboud University [Nijmegen], University of Barcelona, Garvan Institute of medical research, Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS), Czech Academy of Sciences [Prague] (CAS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Genetics and IrBio, University of Cambridge [UK] (CAM), Universidade do Porto = University of Porto, Stazione Zoologica Anton Dohrn (SZN), University of St Andrews [Scotland], Sun Yat-Sen University [Guangzhou] (SYSU), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Manchester [Manchester], Université Paris sciences et lettres (PSL), Academia Sinica, RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), University of Cincinnati (UC), University of Bergen (UiB), ANR-16-CE12-0008,CHORELAND,Détermination de la conservation du landscape génomique de régulation au cours de l'embryogenèse des chordés(2016), European Project: 637591,H2020,ERC-2014-STG,NEURAL AS(2015), European Project: 658521,H2020,H2020-MSCA-IF-2014,EVOREL(2016), European Project: 268513,EC:FP7:ERC,ERC-2010-AdG_20100317,GENEVA(2011), European Commission, The Leverhulme Trust, University of St Andrews. School of Biology, University of St Andrews. Marine Alliance for Science & Technology Scotland, University of St Andrews. Scottish Oceans Institute, University of St Andrews. Biomedical Sciences Research Complex, University of Oxford [Oxford], Radboud university [Nijmegen], Garvan Institute of Medical Research, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Universidade do Porto, Commission of the European Communities, Biotechnology and Biological Sciences Research Council (BBSRC), Wellcome Trust, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Departament de Genetica, Facultat de Biologia, Universitat de Barcelona (UB), Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Científicas, Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Max F. Perutz Laboratories, University of Vienna [Vienna], DYnamique et Organisation des GENomes - Equipe de l'IBENS (DYOGEN), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Unité de Biométrie et Intelligence Artificielle (UBIA), Institut National de la Recherche Agronomique (INRA), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Departament de Genètica, Universitat Autònoma de Barcelona [Barcelona] (UAB), Texas A&M University [College Station], Sun Yat-Sen University (SYSU), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sexe et évolution, Département PEGASE [LBBE] (PEGASE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Analyse, Topologie, Probabilités (LATP), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Medical Sciences / Beijing, Institute of Cellular and Organismic Biology, Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, RIKEN, Centre of Excellence in Plant Energy Biology (ARC), Australian National University (ANU)-School of Biochemistry and Molecular Biology, SARS International Centre for Marine Molecular Biology, Modèles en biologie cellulaire et évolutive (MBCE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), European Research Council, Ministerio de Economía y Competitividad (España), Australian Research Council, Maeso, Ignacio [0000-0002-6440-8457], Tena, Juan J [0000-0001-8165-7984], Perry, Malcolm [0000-0001-5228-3434], Wyatt, Christopher DR [0000-0001-8033-2213], de la Calle-Mustienes, Elisa [0000-0002-8975-6503], Bertrand, Stephanie [0000-0002-0689-0126], Naranjo, Silvia [0000-0002-4529-3332], Jimenez-Gancedo, Sandra [0000-0002-2247-1319], Aldea, Daniel [0000-0001-5101-0194], Buono, Lorena [0000-0002-5457-4515], Louis, Alexandra [0000-0001-7032-5650], Balwierz, Piotr J [0000-0002-1548-4605], Aury, Jean-Marc [0000-0003-1718-3010], Albalat, Ricard [0000-0003-0282-9595], Benito-Gutiérrez, Èlia [0000-0003-2435-0948], Cañestro, Cristian [0000-0003-4623-8105], Castro, Filipe [0000-0001-7697-386X], Ferrier, David EK [0000-0003-3247-6233], Schubert, Michael [0000-0002-2341-712X], Seitz, Hervé [0000-0001-8172-5393], Somorjai, Ildiko [0000-0001-5243-6664], Takahashi, Tokiharu [0000-0002-5785-8660], Yu, Jr-Kai [0000-0001-8591-0529], Carninci, Piero [0000-0001-7202-7243], Martinez-Morales, Juan Ramon [0000-0002-4650-4293], Garcia-Fernàndez, Jordi [0000-0001-5677-5970], Lister, Ryan [0000-0001-6637-7239], Escriva, Hector [0000-0001-7577-5028], Irimia, Manuel [0000-0002-2179-2567], Apollo - University of Cambridge Repository, CIIMAR - Centro Interdisciplinar de Investigação Marinha e Ambiental, COMBE, Isabelle, Détermination de la conservation du landscape génomique de régulation au cours de l'embryogenèse des chordés - - CHORELAND2016 - ANR-16-CE12-0008 - AAPG2016 - VALID, Functions and evolutionary impact of transcriptomic novelties in the vertebrate brain - NEURAL AS - - H20202015-04-01 - 2020-03-31 - 637591 - VALID, Evolution of Regulatory Landscapes in Chordates - EVOREL - - H20202016-01-01 - 2017-12-31 - 658521 - VALID, Genome Evolution in the Animal Kingdom - GENEVA - - EC:FP7:ERC2011-06-01 - 2016-05-31 - 268513 - VALID, Institute of Molecular Genetics of the Czech Academy of Sciences, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) - Grenoble, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Marseille (I2M), Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Riken Omics Science Center, Riken Yokohama Institute, Cincinnati Children's Hospital Medical Center, and Computational Regulatory Genomics
- Subjects
Epigenomics ,Branchiostoma ,genetic analysis ,animal cell ,transcriptomics ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,vertebrate ,zebra fish ,histone modification ,Branchiostoma lanceolatum ,ComputingMilieux_MISCELLANEOUS ,comparative study ,Lancelets ,Regulation of gene expression ,DDC model ,DNA methylation ,adult ,Vertebrate ,Genomics ,priority journal ,Science & Technology - Other Topics ,Molecular Developmental Biology ,LANDSCAPES ,whole genome duplication ,Functional genomics ,chordate evolution ,CONSERVATION ,embryo ,gene sequence ,PLURIPOTENCY ,Article ,animal tissue ,03 medical and health sciences ,regulatory genomics ,biology.animal ,genomics ,Humans ,genome ,mouse ,Science & Technology ,Molecular Sequence Annotation ,TRANSGENESIS ,DNA Methylation ,Ancestral expression ,developmental stage ,030104 developmental biology ,hourglass model ,Amfiox ,Evolutionary biology ,molecular genetics ,chromatin ,Subfunctionalization ,transcriptome ,030217 neurology & neurosurgery ,CHROMATIN ,0301 basic medicine ,Branchiostoma Lanceolatum ,Genome ,specialization ,Gene duplication ,Vertebrats ,Promoter Regions, Genetic ,Whole-genome Duplication (WGD) ,Multidisciplinary ,gene control ,BRANCHIOSTOMA-LANCEOLATUM ,innovation ,Multidisciplinary Sciences ,female ,SEQ ,Vertebrates ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Phylotypic Period ,General Science & Technology ,invertebrate ,QH426 Genetics ,Biology ,DNA DEMETHYLATION ,male ,evolution ,Animals ,controlled study ,gene ,QH426 ,multigene family ,Body Patterning ,Vertebrata ,nonhuman ,Amphioxus ,ZEBRAFISH ,gene duplication ,embryo development ,DAS ,biology.organism_classification ,EVOLUTION ,[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,Gene Expression Regulation ,gene expression ,Molecular evolution ,Transcriptome - Abstract
Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that—in vertebrates—over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations., This research was funded primarily by the European Research Council (ERC) under the European Union’s Horizon 2020 and Seventh Framework Program FP7 research and innovation programs (ERC-AdG-LS8-740041 to J.L.G.-S., ERC-StG-LS2-637591 to M.I., a Marie Sklodowska-Curie Grant (658521) to I.M. and a FP7/2007-2013-ERC-268513 to P.W.H.H.), the Spanish Ministerio de Economía y Competitividad (BFU2016-74961-P to J.L.G.-S., RYC-2016-20089 to I.M., BFU2014-55076-P and BFU2017-89201-P to M.I. and BFU2014-55738-REDT to J.L.G.-S, M.I. and J.R.M.-M), the ‘Centro de Excelencia Severo Ochoa 2013-2017’(SEV-2012-0208), the ‘Unidad de Excelencia María de Maetzu 2017-2021’(MDM-2016-0687), the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program FP7 under REA grant agreement number 607142 (DevCom) to J.L.G.-S., and the CNRS and the ANR (ANR16-CE12-0008-01) to H.E. O.B. was supported by an Australian Research Council Discovery Early Career Researcher Award (DECRA; DE140101962).
- Published
- 2018
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48. Modeling of epigenome dynamics identifies transcription factors that mediate Polycomb targeting.
- Author
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Arnold P, Schöler A, Pachkov M, Balwierz PJ, Jørgensen H, Stadler MB, van Nimwegen E, and Schübeler D
- Subjects
- Animals, Binding Sites, Cattle, Cell Differentiation, Chromatin metabolism, Dogs, Genome, Histones metabolism, Horses, Humans, Macaca, Mice, Neurons cytology, Opossums, Promoter Regions, Genetic, Snail Family Transcription Factors, Stem Cells cytology, Transgenes, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Models, Genetic, Polycomb-Group Proteins metabolism, Transcription Factors metabolism
- Abstract
Although changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. To systematically identify transcription factors (TFs) that can direct chromatin changes during cell fate decisions, we model the relationship between genome-wide dynamics of chromatin marks and the local occurrence of computationally predicted TF binding sites. By applying this computational approach to a time course of Polycomb-mediated H3K27me3 marks during neuronal differentiation of murine stem cells, we identify several motifs that likely regulate the dynamics of this chromatin mark. Among these, the sites bound by REST and by the SNAIL family of TFs are predicted to transiently recruit H3K27me3 in neuronal progenitors. We validate these predictions experimentally and show that absence of REST indeed causes loss of H3K27me3 at target promoters in trans, specifically at the neuronal progenitor state. Moreover, using targeted transgenic insertion, we show that promoter fragments containing REST or SNAIL binding sites are sufficient to recruit H3K27me3 in cis, while deletion of these sites results in loss of H3K27me3. These findings illustrate that the occurrence of TF binding sites can determine chromatin dynamics. Local determination of Polycomb activity by REST and SNAIL motifs exemplifies such TF based regulation of chromatin. Furthermore, our results show that key TFs can be identified ab initio through computational modeling of epigenome data sets using a modeling approach that we make readily accessible.
- Published
- 2013
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49. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line.
- Author
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Suzuki H, Forrest AR, van Nimwegen E, Daub CO, Balwierz PJ, Irvine KM, Lassmann T, Ravasi T, Hasegawa Y, de Hoon MJ, Katayama S, Schroder K, Carninci P, Tomaru Y, Kanamori-Katayama M, Kubosaki A, Akalin A, Ando Y, Arner E, Asada M, Asahara H, Bailey T, Bajic VB, Bauer D, Beckhouse AG, Bertin N, Björkegren J, Brombacher F, Bulger E, Chalk AM, Chiba J, Cloonan N, Dawe A, Dostie J, Engström PG, Essack M, Faulkner GJ, Fink JL, Fredman D, Fujimori K, Furuno M, Gojobori T, Gough J, Grimmond SM, Gustafsson M, Hashimoto M, Hashimoto T, Hatakeyama M, Heinzel S, Hide W, Hofmann O, Hörnquist M, Huminiecki L, Ikeo K, Imamoto N, Inoue S, Inoue Y, Ishihara R, Iwayanagi T, Jacobsen A, Kaur M, Kawaji H, Kerr MC, Kimura R, Kimura S, Kimura Y, Kitano H, Koga H, Kojima T, Kondo S, Konno T, Krogh A, Kruger A, Kumar A, Lenhard B, Lennartsson A, Lindow M, Lizio M, Macpherson C, Maeda N, Maher CA, Maqungo M, Mar J, Matigian NA, Matsuda H, Mattick JS, Meier S, Miyamoto S, Miyamoto-Sato E, Nakabayashi K, Nakachi Y, Nakano M, Nygaard S, Okayama T, Okazaki Y, Okuda-Yabukami H, Orlando V, Otomo J, Pachkov M, Petrovsky N, Plessy C, Quackenbush J, Radovanovic A, Rehli M, Saito R, Sandelin A, Schmeier S, Schönbach C, Schwartz AS, Semple CA, Sera M, Severin J, Shirahige K, Simons C, St Laurent G, Suzuki M, Suzuki T, Sweet MJ, Taft RJ, Takeda S, Takenaka Y, Tan K, Taylor MS, Teasdale RD, Tegnér J, Teichmann S, Valen E, Wahlestedt C, Waki K, Waterhouse A, Wells CA, Winther O, Wu L, Yamaguchi K, Yanagawa H, Yasuda J, Zavolan M, Hume DA, Arakawa T, Fukuda S, Imamura K, Kai C, Kaiho A, Kawashima T, Kawazu C, Kitazume Y, Kojima M, Miura H, Murakami K, Murata M, Ninomiya N, Nishiyori H, Noma S, Ogawa C, Sano T, Simon C, Tagami M, Takahashi Y, Kawai J, and Hayashizaki Y
- Subjects
- Base Sequence, Cell Line, Gene Expression Profiling, Humans, Leukemia, Myeloid genetics, Leukemia, Myeloid metabolism, Models, Genetic, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, RNA, Small Interfering metabolism, Cell Differentiation genetics, Cell Proliferation, Gene Regulatory Networks, Transcription, Genetic
- Abstract
Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.
- Published
- 2009
- Full Text
- View/download PDF
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