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1. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author

de Rie, Derek, Abugessaisa, Imad, Alam, Tanvir, Arner, Erik, Arner, Peter, Ashoor, Haitham, Åström, Gaby, Babina, Magda, Bertin, Nicolas, Burroughs, A Maxwell, Carlisle, Ailsa J, Daub, Carsten O, Detmar, Michael, Deviatiiarov, Ruslan, Fort, Alexandre, Gebhard, Claudia, Goldowitz, Daniel, Guhl, Sven, Ha, Thomas J, Harshbarger, Jayson, Hasegawa, Akira, Hashimoto, Kosuke, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly J, Hon, Chung Chau, Huang, Edward, Ishizu, Yuri, Kai, Chieko, Kasukawa, Takeya, Klinken, Peter, Lassmann, Timo, Lecellier, Charles-Henri, Lee, Weonju, Lizio, Marina, Makeev, Vsevolod, Mathelier, Anthony, Medvedeva, Yulia A, Mejhert, Niklas, Mungall, Christopher J, Noma, Shohei, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Persson, Helena, Rizzu, Patrizia, Roudnicky, Filip, Sætrom, Pål, Sato, Hiroki, Severin, Jessica, Shin, Jay W, Swoboda, Rolf K, Tarui, Hiroshi, Toyoda, Hiroo, Vitting-Seerup, Kristoffer, Winteringham, Louise, Yamaguchi, Yoko, Yasuzawa, Kayoko, Yoneda, Misako, Yumoto, Noriko, Zabierowski, Susan, Zhang, Peter G, Wells, Christine A, Summers, Kim M, Kawaji, Hideya, Sandelin, Albin, Rehli, Michael, Hayashizaki, Yoshihide, Carninci, Piero, Forrest, Alistair RR, and de Hoon, Michiel JL

Subjects
Generic health relevance, Good Health and Well Being, Animals, Cells, Cultured, Gene Expression Profiling, Gene Library, High-Throughput Nucleotide Sequencing, Humans, Mice, MicroRNAs, Molecular Sequence Annotation, Promoter Regions, Genetic, FANTOM Consortium
Abstract

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

Published
2017

3. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Author

FANTOM Consortium, Arner, Erik, Daub, Carsten O., Vitting-Seerup, Kristoffer, Andersson, Robin, Lilje, Berit, Drabløs, Finn, Lennartsson, Andreas, Rönnerblad, Michelle, Hrydziuszko, Olga, Vitezic, Morana, Freeman, Tom C., Alhendi, Ahmad M. N., Arner, Peter, Axton, Richard, Baillie, J. Kenneth, Beckhouse, Anthony, Bodega, Beatrice, Briggs, James, Brombacher, Frank, Davis, Margaret, Detmar, Michael, Ehrlund, Anna, Endoh, Mitsuhiro, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Faulkner, Geoffrey J., Ferrai, Carmelo, Fisher, Malcolm E., Forrester, Lesley, Goldowitz, Daniel, Guler, Reto, Ha, Thomas, Hara, Mitsuko, Herlyn, Meenhard, Ikawa, Tomokatsu, Kai, Chieko, Kawamoto, Hiroshi, Khachigian, Levon M., Klinken, S. Peter, Kojima, Soichi, Koseki, Haruhiko, Klein, Sarah, Mejhert, Niklas, Miyaguchi, Ken, Mizuno, Yosuke, Morimoto, Mitsuru, Morris, Kelly J., Mummery, Christine, Nakachi, Yutaka, Ogishima, Soichi, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Qin, Xian-Yang, Roy, Sugata, Sato, Hiroki, Savvi, Suzana, Saxena, Alka, Schwegmann, Anita, Sugiyama, Daisuke, Swoboda, Rolf, Tanaka, Hiroshi, Tomoiu, Andru, Winteringham, Louise N., Wolvetang, Ernst, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Zabierowski, Susan, Zhang, Peter, Abugessaisa, Imad, Bertin, Nicolas, Diehl, Alexander D., Fukuda, Shiro, Furuno, Masaaki, Harshbarger, Jayson, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Ishizu, Yuri, Itoh, Masayoshi, Kawashima, Tsugumi, Kojima, Miki, Kondo, Naoto, Lizio, Marina, Meehan, Terrence F., Mungall, Christopher J., Murata, Mitsuyoshi, Nishiyori-Sueki, Hiromi, Sahin, Serkan, Nagao-Sato, Sayaka, Severin, Jessica, de Hoon, Michiel J. L., Kawai, Jun, Kasukawa, Takeya, Lassmann, Timo, Suzuki, Harukazu, Kawaji, Hideya, Summers, Kim M., Wells, Christine, Hume, David A., Forrest, Alistair R. R., Sandelin, Albin, Carninci, Piero, and Hayashizaki, Yoshihide

Published
2015

4. PAPD5-mediated 3' adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

Author

Boele, Joost, Persson, Helena, Shin, Jay W., Ishizu, Yuri, Newie, Inga S., Søkilde, Rolf, Hawkins, Shannon M., Coarfa, Cristian, Ikeda, Kazuhiro, Takayama, Ken-ichi, Horie-Inoue, Kuniko, Ando, Yoshinari, Burroughs, A. Maxwell, Sasaki, Chihiro, Suzuki, Chizuru, Sakai, Mizuho, Aoki, Shintaro, Ogawa, Ayumi, Hasegawa, Akira, Lizio, Marina, Kaida, Kaoru, Teusink, Bas, Carninci, Piero, Suzuki, Harukazu, Inoue, Satoshi, Gunaratne, Preethi H., Rovira, Carlos, Hayashizaki, Yoshihide, and de Hoon, Michiel J. L.

Published
2014

5. Deep sequencing of short capped RNAs reveals novel families of noncoding RNAs

Author

de Hoon, Michiel, primary, Bonetti, Alessandro, additional, Plessy, Charles, additional, Ando, Yoshinari, additional, Hon, Chung-Chau, additional, Ishizu, Yuri, additional, Itoh, Masayoshi, additional, Kato, Sachi, additional, Lin, Dongyan, additional, Maekawa, Sho, additional, Murata, Mitsuyoshi, additional, Nishiyori, Hiromi, additional, Shin, Jay W., additional, Stolte, Jens, additional, Suzuki, Ana Maria, additional, Tagami, Michihira, additional, Takahashi, Hazuki, additional, Thongjuea, Supat, additional, Forrest, Alistair R.R., additional, Hayashizaki, Yoshihide, additional, Kere, Juha, additional, and Carninci, Piero, additional

Published
2022
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9. GENE REGULATION: Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Author

Arner, Erik, Daub, Carsten O., Vitting-Seerup, Kristoffer, Andersson, Robin, Lilje, Berit, Drabløs, Finn, Lennartsson, Andreas, Rönnerblad, Michelle, Hrydziuszko, Olga, Vitezic, Morana, Freeman, Tom C., Alhendi, Ahmad M. N., Arner, Peter, Axton, Richard, Baillie, Kenneth J., Beckhouse, Anthony, Bodega, Beatrice, Briggs, James, Brombacher, Frank, Davis, Margaret, Detmar, Michael, Ehrlund, Anna, Endoh, Mitsuhiro, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Faulkner, Geoffrey J., Ferrai, Carmelo, Fisher, Malcolm E., Forrester, Lesley, Goldowitz, Daniel, Guler, Reto, Ha, Thomas, Hara, Mitsuko, Herlyn, Meenhard, Ikawa, Tomokatsu, Kai, Chieko, Kawamoto, Hiroshi, Khachigian, Levon M., Klinken, Peter S., Kojima, Soichi, Koseki, Haruhiko, Klein, Sarah, Mejhert, Niklas, Miyaguchi, Ken, Mizuno, Yosuke, Morimoto, Mitsuru, Morris, Kelly J., Mummery, Christine, Nakachi, Yutaka, Ogishima, Soichi, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Qin, Xian-Yang, Roy, Sugata, Sato, Hiroki, Savvi, Suzana, Saxena, Alka, Schwegmann, Anita, Sugiyama, Daisuke, Swoboda, Rolf, Tanaka, Hiroshi, Tomoiu, Andru, Winteringham, Louise N., Wolvetang, Ernst, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Zabierowski, Susan, Zhang, Peter, Abugessaisa, Imad, Bertin, Nicolas, Diehl, Alexander D., Fukuda, Shiro, Furuno, Masaaki, Harshbarger, Jayson, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Ishizu, Yuri, Itoh, Masayoshi, Kawashima, Tsugumi, Kojima, Miki, Kondo, Naoto, Lizio, Marina, Meehan, Terrence F., Mungall, Christopher J., Murata, Mitsuyoshi, Nishiyori-Sueki, Hiromi, Sahin, Serkan, Nagao-Sato, Sayaka, Severin, Jessica, de Hoon, Michiel J. L., Kawai, Jun, Kasukawa, Takeya, Lassmann, Timo, Suzuki, Harukazu, Kawaji, Hideya, Summers, Kim M., Wells, Christine, Hume, David A., Forrest, Alistair R. R., Sandelin, Albin, Carninci, Piero, and Hayashizaki, Yoshihide

Published
2015
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10. A promoter-level mammalian expression atlas

Author

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

Published
2014
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11. An atlas of active enhancers across human cell types and tissues

Author

Andersson, Robin, Gebhard, Claudia, Miguel-Escalada, Irene, Hoof, Ilka, Bornholdt, Jette, Boyd, Mette, Chen, Yun, Zhao, Xiaobei, Schmidl, Christian, Suzuki, Takahiro, Ntini, Evgenia, Arner, Erik, Valen, Eivind, Li, Kang, Schwarzfischer, Lucia, Glatz, Dagmar, Raithel, Johanna, Lilje, Berit, Rapin, Nicolas, Bagger, Frederik Otzen, Jørgensen, Mette, Andersen, Peter Refsing, Bertin, Nicolas, Rackham, Owen, Burroughs, Maxwell A., Baillie, Kenneth J., Ishizu, Yuri, Shimizu, Yuri, Furuhata, Erina, Maeda, Shiori, Negishi, Yutaka, Mungall, Christopher J., Meehan, Terrence F., Lassmann, Timo, Itoh, Masayoshi, Kawaji, Hideya, Kondo, Naoto, Kawai, Jun, Lennartsson, Andreas, Daub, Carsten O., Heutink, Peter, Hume, David A., Jensen, Torben Heick, Suzuki, Harukazu, Hayashizaki, Yoshihide, Müller, Ferenc, Consortium, The FANTOM, Forrest, Alistair R. R., Carninci, Piero, Rehli, Michael, and Sandelin, Albin

Published
2014
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13. Comparative transcriptomics of primary cells in vertebrates

Author

Alam, Tanvir, primary, Agrawal, Saumya, additional, Severin, Jessica, additional, Young, Robert S., additional, Andersson, Robin, additional, Arner, Erik, additional, Hasegawa, Akira, additional, Lizio, Marina, additional, Ramilowski, Jordan A., additional, Abugessaisa, Imad, additional, Ishizu, Yuri, additional, Noma, Shohei, additional, Tarui, Hiroshi, additional, Taylor, Martin S., additional, Lassmann, Timo, additional, Itoh, Masayoshi, additional, Kasukawa, Takeya, additional, Kawaji, Hideya, additional, Marchionni, Luigi, additional, Sheng, Guojun, additional, R.R. Forrest, Alistair, additional, Khachigian, Levon M., additional, Hayashizaki, Yoshihide, additional, Carninci, Piero, additional, and de Hoon, Michiel J.L., additional

Published
2020
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14. Exciton Primer-Mediated SNP Detection in SmartAmp2 Reactions

Author

Lezhava, Alexander, Ishidao, Takefumi, Ishizu, Yuri, Naito, Kana, Hanami, Takeshi, Katayama, Atsuko, Kogo, Yasushi, Soma, Takahiro, Ikeda, Shuji, Murakami, Kayoko, Nogawa, Chihiro, Itoh, Masayoshi, Mitani, Yasumasa, Harbers, Matthias, Okamoto, Akimitsu, and Hayashizaki, Yoshihide

Published
2010
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15. Comparative transcriptomics of primary cells in vertebrates

Author

Alam, Tanvir, Agrawal, Saumya, Severin, Jessica, Young, Robert S., Andersson, Robin, Arner, Erik, Hasegawa, Akira, Lizio, Marina, Ramilowski, Jordan A., Abugessaisa, Imad, Ishizu, Yuri, Noma, Shohei, Tarui, Hiroshi, Taylor, Martin S., Lassmann, Timo, Itoh, Masayoshi, Kasukawa, Takeya, Kawaji, Hideya, Marchionni, Luigi, Sheng, Guojun, Forrest, Alistair R. R., Khachigian, Levon M., Hayashizaki, Yoshihide, Carninci, Piero, de Hoon, Michiel J. L., Alam, Tanvir, Agrawal, Saumya, Severin, Jessica, Young, Robert S., Andersson, Robin, Arner, Erik, Hasegawa, Akira, Lizio, Marina, Ramilowski, Jordan A., Abugessaisa, Imad, Ishizu, Yuri, Noma, Shohei, Tarui, Hiroshi, Taylor, Martin S., Lassmann, Timo, Itoh, Masayoshi, Kasukawa, Takeya, Kawaji, Hideya, Marchionni, Luigi, Sheng, Guojun, Forrest, Alistair R. R., Khachigian, Levon M., Hayashizaki, Yoshihide, Carninci, Piero, and de Hoon, Michiel J. L.

Abstract

Gene expression profiles in homologous tissues have been observed to be different between species, which may be due to differences between species in the gene expression program in each cell type, but may also reflect differences in cell type composition of each tissue in different species. Here, we compare expression profiles in matching primary cells in human, mouse, rat, dog, and chicken using Cap Analysis Gene Expression (CAGE) and short RNA (sRNA) sequencing data from FANTOM5. While we find that expression profiles of orthologous genes in different species are highly correlated across cell types, in each cell type many genes were differentially expressed between species. Expression of genes with products involved in transcription, RNA processing, and transcriptional regulation was more likely to be conserved, while expression of genes encoding proteins involved in intercellular communication was more likely to have diverged during evolution. Conservation of expression correlated positively with the evolutionary age of genes, suggesting that divergence in expression levels of genes critical for cell function was restricted during evolution. Motif activity analysis showed that both promoters and enhancers are activated by the same transcription factors in different species. An analysis of expression levels of mature miRNAs and of primary miRNAs identified by CAGE revealed that evolutionary old miRNAs are more likely to have conserved expression patterns than young miRNAs. We conclude that key aspects of the regulatory network are conserved, while differential expression of genes involved in cell-to-cell communication may contribute greatly to phenotypic differences between species.

Published
2020

16. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author

de Rie, Yoko, Abugessaisa, Yoko, Alam, Tanvir, Arner, Yoko, Arner, Peter, Ha, Haitham, Aström, Gaby, Babina, Magda, Bertin, Yoko, Burroughs, Yoko, Carlisle, Ailsa, Daub, Yoko, Detmar, Michael, Deviatiiarov, Yoko, Fort, Yoko, Gebhard, Claudia, Goldowitz, Daniel, Guhl, Sven, Ha, Thomas, Harshbarger, Yoko, Hasegawa, Yoko, Hashimoto, Yoko, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly, Hon, Yoko, Huang, Edward, Ishizu, Yoko, Kai, Chieko, Kasukawa, Yoko, Klinken, Peter, Lassmann, Yoko, Lecellier, Charles-Henri, Lee, Weonju, Lizio, Yoko, Makeev, Vsevolod, Mathelier, Anthony, Medvedeva, Yulia, Mejhert, Niklas, Mungall, Christopher, Noma, Yoko, Ohshima, Mitsuhiro, Okada-Hatakeyama, Yoko, Persson, Helena, Rizzu, Patrizia, Roudnicky, Filip, Sætrom, Pål, Sato, Hiroki, Severin, Yoko, Shin, Yoko, Swoboda, Rolf, Tarui, Yoko, Toyoda, Hiroo, Vitting-Seerup, Kristoffer, Winteringham, Louise, Yamaguchi, Yoko, Yasuzawa, Kayoko, Yoneda, Misako, Yumoto, Noriko, Zabierowski, Susan, Zhang, Peter, Wells, Christine, Summers, Kim, Kawaji, Hideya, Sandelin, Albin, Rehli, Michael, Hayashizaki, Yoshihide, Carninci, Piero, Forrest, Alistair, de Hoon, Michiel, de Rie, Derek, Abugessaisa, Imad, Arner, Erik, Ashoor, Haitham, Bertin, Nicolas, Burroughs, A Maxwell, Daub, Carsten, Deviatiiarov, Ruslan, Fort, Alexandre, Ha, Jayson, Ha, Akira, Ha, Kosuke, Hon, Chung Chau, Ishizu, Yuri, Kasukawa, Takeya, Lassmann, Timo, Lizio, Marina, Noma, Shohei, Ha, Mariko, Severin, Jessica, Shin, Jay, Tarui, Hiroshi, Ha, Yoshihide, Computat Biosci Res Ctr, Comp Elect & Math Sci & Engn Div, King Abdullah University of Science and Technology (KAUST), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Dept Dermatol & Allergy, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Clinical Genetics, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institute of Genetics and Selection of Industrial Microorganisms, GosNIIGenetika, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Oncology, Lund University [Lund]-Clinical Sciences, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), University of Copenhagen = Københavns Universitet (KU), Cold Spring Harbor Laboratory, RIKEN Center for Life Science Technologies (RIKEN CLST), Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, Karolinska Institutet [Stockholm], Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Riken Omics Science Center, and Riken Yokohama Institute

Subjects
0301 basic medicine, FANTOM Consortium, Cells, Biomedical Engineering, Bioengineering, Biology, Applied Microbiology and Biotechnology, Genome, Article, Promoter Regions, 03 medical and health sciences, Mice, Genetic, Transcription (biology), metabolism [MicroRNAs], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Gene expression, Transcriptional regulation, Gene silencing, Animals, Humans, genetics [MicroRNAs], Promoter Regions, Genetic, Cells, Cultured, Gene Library, Genetics, Cultured, Gene Expression Profiling, RNA, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, Gene expression profiling, MicroRNAs, 030104 developmental biology, Good Health and Well Being, genetics [Promoter Regions, Genetic], ddc:660, Molecular Medicine, Generic health relevance, Biotechnology, methods [Gene Expression Profiling]
Abstract

International audience; MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

Published
2017
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17. Data Descriptor : FANTOM5 CAGE profiles of human and mouse samples

Author

Noguchi, Shuhei, Arakawa, Takahiro, Fukuda, Shiro, Furuno, Masaaki, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Kaida, Kaoru, Kaiho, Ai, Kanamori-Katayama, Mutsumi, Kawashima, Tsugumi, Kojima, Miki, Kubosaki, Atsutaka, Manabe, Ri-ichiroh, Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakazato, Kenichi, Ninomiya, Noriko, Nishiyori-Sueki, Hiromi, Noma, Shohei, Saijyo, Eri, Saka, Akiko, Sakai, Mizuho, Simon, Christophe, Suzuki, Naoko, Tagami, Michihira, Watanabe, Shoko, Yoshida, Shigehiro, Arner, Peter, Axton, Richard A., Babina, Magda, Baillie, J. Kenneth, Barnett, Timothy C., Beckhouse, Anthony G., Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Carlisle, Ailsa J., Clevers, Hans C., Davis, Carrie A., Detmar, Michael, Dohi, Taeko, Edge, Albert S. B., Edinger, Matthias, Ehrlund, Anna, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Farach-Carson, Mary C., Faulkner, Geoffrey J., Ferrai, Carmelo, Fisher, Malcolm E., Forrester, Lesley M., Fujita, Rie, Furusawa, Jun-ichi, Geijtenbeek, Teunis B., Gingeras, Thomas, Goldowitz, Daniel, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J., Hamaguchi, Masahide, Hara, Mitsuko, Hasegawa, Yuki, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly J., Hume, David A., Ikawa, Tomokatsu, Ishizu, Yuri, Kai, Chieko, Kawamoto, Hiroshi, Kawamura, Yuki I., Kempfle, Judith S., Kenna, Tony J., Kere, Juha, Khachigian, Levon M., Kitamura, Toshio, Klein, Sarah, Klinken, S. Peter, Knox, Alan J., Kojima, Soichi, Koseki, Haruhiko, Koyasu, Shigeo, Lee, Weonju, Lennartsson, Andreas, Mackay-sim, Alan, Mejhert, Niklas, Mizuno, Yosuke, Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Morris, Kelly J., Motohashi, Hozumi, Mummery, Christine L., Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A., Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Pradhan-Bhatt, Swati, Qin, Xian-Yang, Rehli, Michael, Rizzu, Patrizia, Roy, Sugata, Sajantila, Antti, Sakaguchi, Shimon, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schmidl, Christian, Schneider, Claudio, Schulze-Tanzil, Gundula G., Schwegmann, Anita, Sheng, Guojun, Shin, Jay W., Sugiyama, Daisuke, Sugiyama, Takaaki, Summers, Kim M., Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tomoiu, Andru, Toyoda, Hiroo, van de Wetering, Marc, van den Berg, Linda M., Verardo, Roberto, Vijayan, Dipti, Wells, Christine A., Winteringham, Louise N., Wolvetang, Ernst, Yamaguchi, Yoko, Yamamoto, Masayuki, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Yonekura, Yohei, Zhang, Peter G., Zucchelli, Silvia, Abugessaisa, Imad, Arner, Erik, Harshbarger, Jayson, Kondo, Atsushi, Lassmann, Timo, Lizio, Marina, Sahin, Serkan, Sengstag, Thierry, Severin, Jessica, Shimoji, Hisashi, Suzuki, Masanori, Suzuki, Harukazu, Kawai, Jun, Kondo, Naoto, Itoh, Masayoshi, Daub, Carsten O., Kasukawa, Takeya, Kawaji, Hideya, Carninci, Piero, Forrest, Alistair R. R., Hayashizaki, Yoshihide, Medicum, University of Helsinki, Forensic Medicine, Department of Forensic Medicine, and PaleOmics Laboratory

Subjects
ENHANCERS, MAMMALIAN-CELLS, UCSC GENOME BROWSER, VISUALIZATION, UPDATE, GROWTH, IN-VITRO, TRANSCRIPTION, 3111 Biomedicine, ATLAS, GENE-EXPRESSION
Abstract

In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

Published
2017

18. FANTOM5 CAGE profiles of human and mouse samples

Author

Noguchi, Shuhei, primary, Arakawa, Takahiro, additional, Fukuda, Shiro, additional, Furuno, Masaaki, additional, Hasegawa, Akira, additional, Hori, Fumi, additional, Ishikawa-Kato, Sachi, additional, Kaida, Kaoru, additional, Kaiho, Ai, additional, Kanamori-Katayama, Mutsumi, additional, Kawashima, Tsugumi, additional, Kojima, Miki, additional, Kubosaki, Atsutaka, additional, Manabe, Ri-ichiroh, additional, Murata, Mitsuyoshi, additional, Nagao-Sato, Sayaka, additional, Nakazato, Kenichi, additional, Ninomiya, Noriko, additional, Nishiyori-Sueki, Hiromi, additional, Noma, Shohei, additional, Saijyo, Eri, additional, Saka, Akiko, additional, Sakai, Mizuho, additional, Simon, Christophe, additional, Suzuki, Naoko, additional, Tagami, Michihira, additional, Watanabe, Shoko, additional, Yoshida, Shigehiro, additional, Arner, Peter, additional, Axton, Richard A., additional, Babina, Magda, additional, Baillie, J. Kenneth, additional, Barnett, Timothy C., additional, Beckhouse, Anthony G., additional, Blumenthal, Antje, additional, Bodega, Beatrice, additional, Bonetti, Alessandro, additional, Briggs, James, additional, Brombacher, Frank, additional, Carlisle, Ailsa J., additional, Clevers, Hans C., additional, Davis, Carrie A., additional, Detmar, Michael, additional, Dohi, Taeko, additional, Edge, Albert S.B., additional, Edinger, Matthias, additional, Ehrlund, Anna, additional, Ekwall, Karl, additional, Endoh, Mitsuhiro, additional, Enomoto, Hideki, additional, Eslami, Afsaneh, additional, Fagiolini, Michela, additional, Fairbairn, Lynsey, additional, Farach-Carson, Mary C., additional, Faulkner, Geoffrey J., additional, Ferrai, Carmelo, additional, Fisher, Malcolm E., additional, Forrester, Lesley M., additional, Fujita, Rie, additional, Furusawa, Jun-ichi, additional, Geijtenbeek, Teunis B., additional, Gingeras, Thomas, additional, Goldowitz, Daniel, additional, Guhl, Sven, additional, Guler, Reto, additional, Gustincich, Stefano, additional, Ha, Thomas J., additional, Hamaguchi, Masahide, additional, Hara, Mitsuko, additional, Hasegawa, Yuki, additional, Herlyn, Meenhard, additional, Heutink, Peter, additional, Hitchens, Kelly J., additional, Hume, David A., additional, Ikawa, Tomokatsu, additional, Ishizu, Yuri, additional, Kai, Chieko, additional, Kawamoto, Hiroshi, additional, Kawamura, Yuki I., additional, Kempfle, Judith S., additional, Kenna, Tony J., additional, Kere, Juha, additional, Khachigian, Levon M., additional, Kitamura, Toshio, additional, Klein, Sarah, additional, Klinken, S. Peter, additional, Knox, Alan J., additional, Kojima, Soichi, additional, Koseki, Haruhiko, additional, Koyasu, Shigeo, additional, Lee, Weonju, additional, Lennartsson, Andreas, additional, Mackay-sim, Alan, additional, Mejhert, Niklas, additional, Mizuno, Yosuke, additional, Morikawa, Hiromasa, additional, Morimoto, Mitsuru, additional, Moro, Kazuyo, additional, Morris, Kelly J., additional, Motohashi, Hozumi, additional, Mummery, Christine L., additional, Nakachi, Yutaka, additional, Nakahara, Fumio, additional, Nakamura, Toshiyuki, additional, Nakamura, Yukio, additional, Nozaki, Tadasuke, additional, Ogishima, Soichi, additional, Ohkura, Naganari, additional, Ohno, Hiroshi, additional, Ohshima, Mitsuhiro, additional, Okada-Hatakeyama, Mariko, additional, Okazaki, Yasushi, additional, Orlando, Valerio, additional, Ovchinnikov, Dmitry A., additional, Passier, Robert, additional, Patrikakis, Margaret, additional, Pombo, Ana, additional, Pradhan-Bhatt, Swati, additional, Qin, Xian-Yang, additional, Rehli, Michael, additional, Rizzu, Patrizia, additional, Roy, Sugata, additional, Sajantila, Antti, additional, Sakaguchi, Shimon, additional, Sato, Hiroki, additional, Satoh, Hironori, additional, Savvi, Suzana, additional, Saxena, Alka, additional, Schmidl, Christian, additional, Schneider, Claudio, additional, Schulze-Tanzil, Gundula G., additional, Schwegmann, Anita, additional, Sheng, Guojun, additional, Shin, Jay W., additional, Sugiyama, Daisuke, additional, Sugiyama, Takaaki, additional, Summers, Kim M., additional, Takahashi, Naoko, additional, Takai, Jun, additional, Tanaka, Hiroshi, additional, Tatsukawa, Hideki, additional, Tomoiu, Andru, additional, Toyoda, Hiroo, additional, van de Wetering, Marc, additional, van den Berg, Linda M., additional, Verardo, Roberto, additional, Vijayan, Dipti, additional, Wells, Christine A., additional, Winteringham, Louise N., additional, Wolvetang, Ernst, additional, Yamaguchi, Yoko, additional, Yamamoto, Masayuki, additional, Yanagi-Mizuochi, Chiyo, additional, Yoneda, Misako, additional, Yonekura, Yohei, additional, Zhang, Peter G., additional, Zucchelli, Silvia, additional, Abugessaisa, Imad, additional, Arner, Erik, additional, Harshbarger, Jayson, additional, Kondo, Atsushi, additional, Lassmann, Timo, additional, Lizio, Marina, additional, Sahin, Serkan, additional, Sengstag, Thierry, additional, Severin, Jessica, additional, Shimoji, Hisashi, additional, Suzuki, Masanori, additional, Suzuki, Harukazu, additional, Kawai, Jun, additional, Kondo, Naoto, additional, Itoh, Masayoshi, additional, Daub, Carsten O., additional, Kasukawa, Takeya, additional, Kawaji, Hideya, additional, Carninci, Piero, additional, Forrest, Alistair R.R., additional, and Hayashizaki, Yoshihide, additional

Published
2017
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19. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

Author

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.

Published
2015
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20. FANTOM5 CAGE profiles of human and mouse samples

Author

Noguchi, Shuhei, Arakawa, Takahiro, Fukuda, Shiro, Furuno, Masaaki, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Kaida, Kaoru, Kaiho, Ai, Kanamori-Katayama, Mutsumi, Kawashima, Tsugumi, Kojima, Miki, Kubosaki, Atsutaka, Manabe, Ri-ichiroh, Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakazato, Kenichi, Ninomiya, Noriko, Nishiyori-Sueki, Hiromi, Noma, Shohei, Saijyo, Eri, Saka, Akiko, Sakai, Mizuho, Simon, Christophe, Suzuki, Naoko, Tagami, Michihira, Watanabe, Shoko, Yoshida, Shigehiro, Arner, Peter, Axton, Richard A, Babina, Magda, Baillie, J Kenneth, Barnett, Timothy C, Beckhouse, Anthony G, Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Carlisle, Ailsa J, Clevers, Hans C, Davis, Carrie A, Detmar, Michael, Dohi, Taeko, Edge, Albert S B, Edinger, Matthias, Ehrlund, Anna, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Farach-Carson, Mary C, Faulkner, Geoffrey J, Ferrai, Carmelo, Fisher, Malcolm E, Forrester, Lesley M, Fujita, Rie, Furusawa, Jun-ichi, Geijtenbeek, Teunis B, Gingeras, Thomas, Goldowitz, Daniel, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J, Hamaguchi, Masahide, Hara, Mitsuko, Hasegawa, Yuki, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly J, Hume, David A, Ikawa, Tomokatsu, Ishizu, Yuri, Kai, Chieko, Kawamoto, Hiroshi, Kawamura, Yuki I, Kempfle, Judith S, Kenna, Tony J, Kere, Juha, Khachigian, Levon M, Kitamura, Toshio, Klein, Sarah, Klinken, S Peter, Knox, Alan J, Kojima, Soichi, Koseki, Haruhiko, Koyasu, Shigeo, Lee, Weonju, Lennartsson, Andreas, Mackay-Sim, Alan, Mejhert, Niklas, Mizuno, Yosuke, Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Morris, Kelly J, Motohashi, Hozumi, Mummery, Christine L, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Pradhan-Bhatt, Swati, Qin, Xian-Yang, Rehli, Michael, Rizzu, Patrizia, Roy, Sugata, Sajantila, Antti, Sakaguchi, Shimon, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schmidl, Christian, Schneider, Claudio, Schulze-Tanzil, Gundula G, Schwegmann, Anita, Sheng, Guojun, Shin, Jay W, Sugiyama, Daisuke, Sugiyama, Takaaki, Summers, Kim M, Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tomoiu, Andru, Toyoda, Hiroo, van de Wetering, Marc, van den Berg, Linda M, Verardo, Roberto, Vijayan, Dipti, Wells, Christine A, Winteringham, Louise N, Wolvetang, Ernst, Yamaguchi, Yoko, Yamamoto, Masayuki, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Yonekura, Yohei, Zhang, Peter G, Zucchelli, Silvia, Abugessaisa, Imad, Arner, Erik, Harshbarger, Jayson, Kondo, Atsushi, Lassmann, Timo, Lizio, Marina, Sahin, Serkan, Sengstag, Thierry, Severin, Jessica, Shimoji, Hisashi, Suzuki, Masanori, Suzuki, Harukazu, Kawai, Jun, Kondo, Naoto, Itoh, Masayoshi, Daub, Carsten O, Kasukawa, Takeya, Kawaji, Hideya, Carninci, Piero, Forrest, Alistair R R, Hayashizaki, Yoshihide, Noguchi, Shuhei, Arakawa, Takahiro, Fukuda, Shiro, Furuno, Masaaki, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Kaida, Kaoru, Kaiho, Ai, Kanamori-Katayama, Mutsumi, Kawashima, Tsugumi, Kojima, Miki, Kubosaki, Atsutaka, Manabe, Ri-ichiroh, Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakazato, Kenichi, Ninomiya, Noriko, Nishiyori-Sueki, Hiromi, Noma, Shohei, Saijyo, Eri, Saka, Akiko, Sakai, Mizuho, Simon, Christophe, Suzuki, Naoko, Tagami, Michihira, Watanabe, Shoko, Yoshida, Shigehiro, Arner, Peter, Axton, Richard A, Babina, Magda, Baillie, J Kenneth, Barnett, Timothy C, Beckhouse, Anthony G, Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Carlisle, Ailsa J, Clevers, Hans C, Davis, Carrie A, Detmar, Michael, Dohi, Taeko, Edge, Albert S B, Edinger, Matthias, Ehrlund, Anna, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Farach-Carson, Mary C, Faulkner, Geoffrey J, Ferrai, Carmelo, Fisher, Malcolm E, Forrester, Lesley M, Fujita, Rie, Furusawa, Jun-ichi, Geijtenbeek, Teunis B, Gingeras, Thomas, Goldowitz, Daniel, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J, Hamaguchi, Masahide, Hara, Mitsuko, Hasegawa, Yuki, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly J, Hume, David A, Ikawa, Tomokatsu, Ishizu, Yuri, Kai, Chieko, Kawamoto, Hiroshi, Kawamura, Yuki I, Kempfle, Judith S, Kenna, Tony J, Kere, Juha, Khachigian, Levon M, Kitamura, Toshio, Klein, Sarah, Klinken, S Peter, Knox, Alan J, Kojima, Soichi, Koseki, Haruhiko, Koyasu, Shigeo, Lee, Weonju, Lennartsson, Andreas, Mackay-Sim, Alan, Mejhert, Niklas, Mizuno, Yosuke, Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Morris, Kelly J, Motohashi, Hozumi, Mummery, Christine L, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Pradhan-Bhatt, Swati, Qin, Xian-Yang, Rehli, Michael, Rizzu, Patrizia, Roy, Sugata, Sajantila, Antti, Sakaguchi, Shimon, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schmidl, Christian, Schneider, Claudio, Schulze-Tanzil, Gundula G, Schwegmann, Anita, Sheng, Guojun, Shin, Jay W, Sugiyama, Daisuke, Sugiyama, Takaaki, Summers, Kim M, Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tomoiu, Andru, Toyoda, Hiroo, van de Wetering, Marc, van den Berg, Linda M, Verardo, Roberto, Vijayan, Dipti, Wells, Christine A, Winteringham, Louise N, Wolvetang, Ernst, Yamaguchi, Yoko, Yamamoto, Masayuki, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Yonekura, Yohei, Zhang, Peter G, Zucchelli, Silvia, Abugessaisa, Imad, Arner, Erik, Harshbarger, Jayson, Kondo, Atsushi, Lassmann, Timo, Lizio, Marina, Sahin, Serkan, Sengstag, Thierry, Severin, Jessica, Shimoji, Hisashi, Suzuki, Masanori, Suzuki, Harukazu, Kawai, Jun, Kondo, Naoto, Itoh, Masayoshi, Daub, Carsten O, Kasukawa, Takeya, Kawaji, Hideya, Carninci, Piero, Forrest, Alistair R R, and Hayashizaki, Yoshihide

Abstract

In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

Published
2017

21. An atlas of active enhancers across human cell types and tissues

Author

Boyd, Mette, Lilje, Berit, Glatz, Dagmar, Arner, Erik, Bertin, Nicolas, Rapin, Nicolas, Mungall, Christopher J., Rackham, Owen, Andersson, Robin, Miguel-Escalada, Irene, Bagger, Frederik Otzen, Furuhata, Erina, Chen, Yun, Gebhard, Claudia, Li, Kang, Raithel, Johanna, Ishizu, Yuri, Maeda, Shiori, Hoof, Ilka, Schmidl, Christian, Bornholdt, Jette, Andersen, Peter Refsing, Shimizu, Yuri, Schwarzfischer, Lucia, Jørgensen, Mette, Baillie, J. Kenneth, Negishi, Yutaka, Zhao, Xiaobei, Suzuki, Takahiro, Valen, Eivind, Ntini, Evgenia, and Burroughs, A. Maxwell

Abstract

Enhancers control the correct temporal and cell type-specific activation of gene expression in higher eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. We use the FANTOM5 panel of samples covering the majority of human tissues and cell types to produce an atlas of active, in vivo transcribed enhancers. We show that enhancers share properties with CpG-poor mRNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, identify disease-associated regulatory single nucleotide polymorphisms, and classify cell type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell type-specific enhancers and gene regulation.

Published
2014
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22. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Author

Arner, Erik, Daub, Carsten O., Vitting-Seerup, Kristoffer, Andersson, Robin, Lilje, Berit, Drabløs, Finn, Lennartsson, Andreas, Rönnerblad, Michelle, Hrydziuszko, Olga, Vitezic, Morana, Freeman, Tom C, Alhendi, Ahmad M N, Arner, Peter, Axton, Richard, Baillie, J Kenneth, Beckhouse, Anthony, Bodega, Beatrice, Briggs, James, Brombacher, Frank, Davis, Margaret, Detmar, Michael, Ehrlund, Anna, Endoh, Mitsuhiro, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Faulkner, Geoffrey J, Ferrai, Carmelo, Fisher, Malcolm E, Forrester, Lesley, Goldowitz, Daniel, Guler, Reto, Ha, Thomas, Hara, Mitsuko, Herlyn, Meenhard, Ikawa, Tomokatsu, Kai, Chieko, Kawamoto, Hiroshi, Khachigian, Levon M, Klinken, S Peter, Kojima, Soichi, Koseki, Haruhiko, Klein, Sarah, Mejhert, Niklas, Miyaguchi, Ken, Mizuno, Yosuke, Morimoto, Mitsuru, Morris, Kelly J, Mummery, Christine, Nakachi, Yutaka, Ogishima, Soichi, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Qin, Xian-Yang, Roy, Sugata, Sato, Hiroki, Savvi, Suzana, Saxena, Alka, Schwegmann, Anita, Sugiyama, Daisuke, Swoboda, Rolf, Tanaka, Hiroshi, Tomoiu, Andru, Winteringham, Louise N, Wolvetang, Ernst, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Zabierowski, Susan, Zhang, Peter, Abugessaisa, Imad, Bertin, Nicolas, Diehl, Alexander D, Fukuda, Shiro, Furuno, Masaaki, Harshbarger, Jayson, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Ishizu, Yuri, Itoh, Masayoshi, Kawashima, Tsugumi, Kojima, Miki, Kondo, Naoto, Lizio, Marina, Meehan, Terrence F, Mungall, Christopher J, Murata, Mitsuyoshi, Nishiyori-Sueki, Hiromi, Sahin, Serkan, Nagao-Sato, Sayaka, Severin, Jessica, de Hoon, Michiel J L, Kawai, Jun, Kasukawa, Takeya, Lassmann, Timo, Suzuki, Harukazu, Kawaji, Hideya, Summers, Kim M, Wells, Christine, Hume, David A, Forrest, Alistair R R, Sandelin, Albin Gustav, Carninci, Piero, Hayashizaki, Yoshihide, Arner, Erik, Daub, Carsten O., Vitting-Seerup, Kristoffer, Andersson, Robin, Lilje, Berit, Drabløs, Finn, Lennartsson, Andreas, Rönnerblad, Michelle, Hrydziuszko, Olga, Vitezic, Morana, Freeman, Tom C, Alhendi, Ahmad M N, Arner, Peter, Axton, Richard, Baillie, J Kenneth, Beckhouse, Anthony, Bodega, Beatrice, Briggs, James, Brombacher, Frank, Davis, Margaret, Detmar, Michael, Ehrlund, Anna, Endoh, Mitsuhiro, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Faulkner, Geoffrey J, Ferrai, Carmelo, Fisher, Malcolm E, Forrester, Lesley, Goldowitz, Daniel, Guler, Reto, Ha, Thomas, Hara, Mitsuko, Herlyn, Meenhard, Ikawa, Tomokatsu, Kai, Chieko, Kawamoto, Hiroshi, Khachigian, Levon M, Klinken, S Peter, Kojima, Soichi, Koseki, Haruhiko, Klein, Sarah, Mejhert, Niklas, Miyaguchi, Ken, Mizuno, Yosuke, Morimoto, Mitsuru, Morris, Kelly J, Mummery, Christine, Nakachi, Yutaka, Ogishima, Soichi, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Qin, Xian-Yang, Roy, Sugata, Sato, Hiroki, Savvi, Suzana, Saxena, Alka, Schwegmann, Anita, Sugiyama, Daisuke, Swoboda, Rolf, Tanaka, Hiroshi, Tomoiu, Andru, Winteringham, Louise N, Wolvetang, Ernst, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Zabierowski, Susan, Zhang, Peter, Abugessaisa, Imad, Bertin, Nicolas, Diehl, Alexander D, Fukuda, Shiro, Furuno, Masaaki, Harshbarger, Jayson, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Ishizu, Yuri, Itoh, Masayoshi, Kawashima, Tsugumi, Kojima, Miki, Kondo, Naoto, Lizio, Marina, Meehan, Terrence F, Mungall, Christopher J, Murata, Mitsuyoshi, Nishiyori-Sueki, Hiromi, Sahin, Serkan, Nagao-Sato, Sayaka, Severin, Jessica, de Hoon, Michiel J L, Kawai, Jun, Kasukawa, Takeya, Lassmann, Timo, Suzuki, Harukazu, Kawaji, Hideya, Summers, Kim M, Wells, Christine, Hume, David A, Forrest, Alistair R R, Sandelin, Albin Gustav, Carninci, Piero, and Hayashizaki, Yoshihide

Abstract

Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.

Published
2015

23. A promoter-level mammalian expression atlas

Author

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.

Published
2014

24. A promoter-level mammalian expression atlas

Author

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.

Published
2014

25. One-Step Detection of the 2009 Pandemic Influenza A(H1N1) Virus by the RT-SmartAmp Assay and Its Clinical Validation

Author

Kawai, Yuki, primary, Kimura, Yasumasa, additional, Lezhava, Alexander, additional, Kanamori, Hajime, additional, Usui, Kengo, additional, Hanami, Takeshi, additional, Soma, Takahiro, additional, Morlighem, Jean-Étienne, additional, Saga, Satomi, additional, Ishizu, Yuri, additional, Aoki, Shintaro, additional, Endo, Ryuta, additional, Oguchi-Katayama, Atsuko, additional, Kogo, Yasushi, additional, Mitani, Yasumasa, additional, Ishidao, Takefumi, additional, Kawakami, Chiharu, additional, Kurata, Hideshi, additional, Furuya, Yumiko, additional, Saito, Takayuki, additional, Okazaki, Norio, additional, Chikahira, Masatsugu, additional, Hayashi, Eiji, additional, Tsuruoka, Sei-ichi, additional, Toguchi, Tokumichi, additional, Saito, Yoshitomo, additional, Ban, Toshiaki, additional, Izumi, Shinyu, additional, Uryu, Hideko, additional, Kudo, Koichiro, additional, Sakai-Tagawa, Yuko, additional, Kawaoka, Yoshihiro, additional, Hirai, Aizan, additional, Hayashizaki, Yoshihide, additional, and Ishikawa, Toshihisa, additional

Published
2012
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26. LRRN4 and UPK3B Are Markers of Primary Mesothelial Cells

Author

Kanamori-Katayama, Mutsumi, primary, Kaiho, Ai, additional, Ishizu, Yuri, additional, Okamura-Oho, Yuko, additional, Hino, Okio, additional, Abe, Masaaki, additional, Kishimoto, Takumi, additional, Sekihara, Hisahiko, additional, Nakamura, Yukio, additional, Suzuki, Harukazu, additional, Forrest, Alistair R. R., additional, and Hayashizaki, Yoshihide, additional

Published
2011
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29. Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line.

Author

Lizio M, Ishizu Y, Itoh M, Lassmann T, Hasegawa A, Kubosaki A, Severin J, Kawaji H, Nakamura Y, Suzuki H, Hayashizaki Y, Carninci P, and Forrest AR

Abstract

Mammals are composed of hundreds of different cell types with specialized functions. Each of these cellular phenotypes are controlled by different combinations of transcription factors. Using a human non islet cell insulinoma cell line (TC-YIK) which expresses insulin and the majority of known pancreatic beta cell specific genes as an example, we describe a general approach to identify key cell-type-specific transcription factors (TFs) and their direct and indirect targets. By ranking all human TFs by their level of enriched expression in TC-YIK relative to a broad collection of samples (FANTOM5), we confirmed known key regulators of pancreatic function and development. Systematic siRNA mediated perturbation of these TFs followed by qRT-PCR revealed their interconnections with NEUROD1 at the top of the regulation hierarchy and its depletion drastically reducing insulin levels. For 15 of the TF knock-downs (KD), we then used Cap Analysis of Gene Expression (CAGE) to identify thousands of their targets genome-wide (KD-CAGE). The data confirm NEUROD1 as a key positive regulator in the transcriptional regulatory network (TRN), and ISL1, and PROX1 as antagonists. As a complimentary approach we used ChIP-seq on four of these factors to identify NEUROD1, LMX1A, PAX6, and RFX6 binding sites in the human genome. Examining the overlap between genes perturbed in the KD-CAGE experiments and genes with a ChIP-seq peak within 50 kb of their promoter, we identified direct transcriptional targets of these TFs. Integration of KD-CAGE and ChIP-seq data shows that both NEUROD1 and LMX1A work as the main transcriptional activators. In the core TRN (i.e., TF-TF only), NEUROD1 directly transcriptionally activates the pancreatic TFs HSF4, INSM1, MLXIPL, MYT1, NKX6-3, ONECUT2, PAX4, PROX1, RFX6, ST18, DACH1, and SHOX2, while LMX1A directly transcriptionally activates DACH1, SHOX2, PAX6, and PDX1. Analysis of these complementary datasets suggests the need for caution in interpreting ChIP-seq datasets. (1) A large fraction of binding sites are at distal enhancer sites and cannot be directly associated to their targets, without chromatin conformation data. (2) Many peaks may be non-functional: even when there is a peak at a promoter, the expression of the gene may not be affected in the matching perturbation experiment.

Published
2015
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30. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.

Author

Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drabløs F, Lennartsson A, Rönnerblad M, Hrydziuszko O, Vitezic M, Freeman TC, Alhendi AM, Arner P, Axton R, Baillie JK, Beckhouse A, Bodega B, Briggs J, Brombacher F, Davis M, Detmar M, Ehrlund A, Endoh M, Eslami A, Fagiolini M, Fairbairn L, Faulkner GJ, Ferrai C, Fisher ME, Forrester L, Goldowitz D, Guler R, Ha T, Hara M, Herlyn M, Ikawa T, Kai C, Kawamoto H, Khachigian LM, Klinken SP, Kojima S, Koseki H, Klein S, Mejhert N, Miyaguchi K, Mizuno Y, Morimoto M, Morris KJ, Mummery C, Nakachi Y, Ogishima S, Okada-Hatakeyama M, Okazaki Y, Orlando V, Ovchinnikov D, Passier R, Patrikakis M, Pombo A, Qin XY, Roy S, Sato H, Savvi S, Saxena A, Schwegmann A, Sugiyama D, Swoboda R, Tanaka H, Tomoiu A, Winteringham LN, Wolvetang E, Yanagi-Mizuochi C, Yoneda M, Zabierowski S, Zhang P, Abugessaisa I, Bertin N, Diehl AD, Fukuda S, Furuno M, Harshbarger J, Hasegawa A, Hori F, Ishikawa-Kato S, Ishizu Y, Itoh M, Kawashima T, Kojima M, Kondo N, Lizio M, Meehan TF, Mungall CJ, Murata M, Nishiyori-Sueki H, Sahin S, Nagao-Sato S, Severin J, de Hoon MJ, Kawai J, Kasukawa T, Lassmann T, Suzuki H, Kawaji H, Summers KM, Wells C, Hume DA, Forrest AR, Sandelin A, Carninci P, and Hayashizaki Y

Subjects
Animals, Binding Sites, Cattle, Dogs, Mice, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Stem Cells metabolism, Cell Differentiation genetics, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Stem Cells cytology, Transcription Factors metabolism, Transcription, Genetic
Abstract

Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation., (Copyright © 2015, American Association for the Advancement of Science.)

Published
2015
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