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1. 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

2. 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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3. Host restriction of avian influenza viruses at the level of the ribonucleoproteins

Author

Naffakh, Nadia, Tomoiu, Andru, Rameix-Welti, Marie-Anne, and van der Werf, Sylvie

Subjects
Disease transmission -- Methods, Host-virus relationships -- Physiological aspects, Avian influenza viruses -- Physiological aspects, Avian influenza viruses -- Genetic aspects, Ribonucleoproteins -- Properties, Biological sciences
Published
2008

4. Comprehensive characterisation of transcriptional activity during influenza A virus infection reveals biases in cap-snatching of host RNA sequences

Author

Clohisey, Sara, Parkinson, Nicholas, Wang, Bo, Bertin, Nicolas, Wise, Helen, Tomoiu, Andru, FANTOM consortium, The, Summers, Kim M, Hendry, Ross W., Carninci, Piero, Forrest, Alistair A., Hayashizaki, Yoshihide, Digard, Paul, Hume, David, and Baillie, Kenneth

Subjects
Lipopolysaccharides, RNA Caps, Transcription, Genetic, Immunology, Biology, medicine.disease_cause, Virus Replication, Microbiology, Deep sequencing, Virus, Cap snatching, 03 medical and health sciences, 0302 clinical medicine, Bias, Virology, RNA, Small Nuclear, Influenza, Human, Influenza A virus, medicine, Humans, Gene Regulatory Networks, RNA, Messenger, Spotlight, 030304 developmental biology, 0303 health sciences, Messenger RNA, Base Sequence, Host Microbial Interactions, Macrophages, RNA, cap-snatching, RNA-Dependent RNA Polymerase, Cap analysis gene expression, 3. Good health, Virus-Cell Interactions, CAGE, Insect Science, NGS, SnRNA transcription, RNA, Viral, influenza, 030217 neurology & neurosurgery
Abstract

Infection with influenza A virus (IAV) infection is responsible for an estimated 500,000 deaths and up to 5 million cases of severe respiratory illness each year. In this study, we looked at human primary immune cells (macrophages) infected with IAV. Our method allows us to look at both the host and the virus in parallel. We used these data to explore a process known as “cap-snatching,” where IAV snatches a short nucleotide sequence from capped host RNA. This process was believed to be random. We demonstrate biased snatching of numerous host RNAs, including those associated with snRNA transcription, and avoidance of host transcripts encoding host ribosomal proteins, which are required by IAV for replication. We then describe the transcriptional landscape of the host response to IAV, observing new features, including a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation, seen in response to other treatments., Macrophages in the lung detect and respond to influenza A virus (IAV), determining the nature of the immune response. Using terminal-depth cap analysis of gene expression (CAGE), we quantified transcriptional activity of both host and pathogen over a 24-h time course of IAV infection in primary human monocyte-derived macrophages (MDMs). This method allowed us to observe heterogenous host sequences incorporated into IAV mRNA, “snatched” 5′ RNA caps, and corresponding RNA sequences from host RNAs. In order to determine whether cap-snatching is random or exhibits a bias, we systematically compared host sequences incorporated into viral mRNA (“snatched”) against a complete survey of all background host RNA in the same cells, at the same time. Using a computational strategy designed to eliminate sources of bias due to read length, sequencing depth, and multimapping, we were able to quantify overrepresentation of host RNA features among the sequences that were snatched by IAV. We demonstrate biased snatching of numerous host RNAs, particularly small nuclear RNAs (snRNAs), and avoidance of host transcripts encoding host ribosomal proteins, which are required by IAV for replication. We then used a systems approach to describe the transcriptional landscape of the host response to IAV, observing many new features, including a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation, seen in response to other treatments. IMPORTANCE Infection with influenza A virus (IAV) infection is responsible for an estimated 500,000 deaths and up to 5 million cases of severe respiratory illness each year. In this study, we looked at human primary immune cells (macrophages) infected with IAV. Our method allows us to look at both the host and the virus in parallel. We used these data to explore a process known as “cap-snatching,” where IAV snatches a short nucleotide sequence from capped host RNA. This process was believed to be random. We demonstrate biased snatching of numerous host RNAs, including those associated with snRNA transcription, and avoidance of host transcripts encoding host ribosomal proteins, which are required by IAV for replication. We then describe the transcriptional landscape of the host response to IAV, observing new features, including a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation, seen in response to other treatments.

Published
2020

9. A gene expression atlas of the domestic pig

Author

Freeman Tom C, Ivens Alasdair, Baillie J Kenneth, Beraldi Dario, Barnett Mark W, Dorward David, Downing Alison, Fairbairn Lynsey, Kapetanovic Ronan, Raza Sobia, Tomoiu Andru, Alberio Ramiro, Wu Chunlei, Su Andrew I, Summers Kim M, Tuggle Christopher K, Archibald Alan L, and Hume David A

Subjects
pig, porcine, Sus scrofa, microarray, transcriptome, transcription network, pathway, gastrointestinal tract, Biology (General), QH301-705.5
Abstract

Abstract Background This work describes the first genome-wide analysis of the transcriptional landscape of the pig. A new porcine Affymetrix expression array was designed in order to provide comprehensive coverage of the known pig transcriptome. The new array was used to generate a genome-wide expression atlas of pig tissues derived from 62 tissue/cell types. These data were subjected to network correlation analysis and clustering. Results The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed. We describe the overall transcriptional signatures present in the tissue atlas, where possible assigning those signatures to specific cell populations or pathways. In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human. We identify sets of genes that define specialized cellular compartments and region-specific digestive functions. Finally, we performed a network analysis of the transcription factors expressed in the gastrointestinal tract and demonstrate how they sub-divide into functional groups that may control cellular gastrointestinal development. Conclusions As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells. The data and analyses are available on the websites http://biogps.org and http://www.macrophages.com/pig-atlas.

Published
2012
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10. 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

12. 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

13. 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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14. 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

19. Recruitment of RED-SMU1 Complex by Influenza A Virus RNA Polymerase to Control Ciral mRNA Splicing.

Author

Fournier, Guillaume, Chiang, Chiayn, Munier, Sandie, Tomoiu, Andru, Demeret, Caroline, Vidalain, Pierre-Olivier, Jacob, Yves, and Naffakh, Nadia

Subjects
INFLUENZA A virus, RNA polymerases, PATHOGENIC microorganisms, MESSENGER RNA, RNA splicing, GENE expression
Abstract

Influenza A viruses are major pathogens in humans and in animals, whose genome consists of eight single-stranded RNA segments of negative polarity. Viral mRNAs are synthesized by the viral RNA-dependent RNA polymerase in the nucleus of infected cells, in close association with the cellular transcriptional machinery. Two proteins essential for viral multiplication, the exportin NS2/NEP and the ion channel protein M2, are produced by splicing of the NS1 and M1 mRNAs, respectively. Here we identify two human spliceosomal factors, RED and SMU1, that control the expression of NS2/NEP and are required for efficient viral multiplication. We provide several lines of evidence that in infected cells, the hetero-trimeric viral polymerase recruits a complex formed by RED and SMU1 through interaction with its PB2 and PB1 subunits. We demonstrate that the splicing of the NS1 viral mRNA is specifically affected in cells depleted of RED or SMU1, leading to a decreased production of the spliced mRNA species NS2, and to a reduced NS2/NS1 protein ratio. In agreement with the exportin function of NS2, these defects impair the transport of newly synthesized viral ribonucleoproteins from the nucleus to the cytoplasm, and strongly reduce the production of infectious influenza virions. Overall, our results unravel a new mechanism of viral subversion of the cellular splicing machinery, by establishing that the human splicing factors RED and SMU1 act jointly as key regulators of influenza virus gene expression. In addition, our data point to a central role of the viral RNA polymerase in coupling transcription and alternative splicing of the viral mRNAs. [ABSTRACT FROM AUTHOR]

Published
2014
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20. Comprehensive Characterization of Transcriptional Activity during Influenza A Virus Infection Reveals Biases in Cap-Snatching of Host RNA Sequences.

Author

Clohisey S, Parkinson N, Wang B, Bertin N, Wise H, Tomoiu A, Summers KM, Hendry RW, Carninci P, Forrest ARR, Hayashizaki Y, Digard P, Hume DA, and Baillie JK

Subjects
Bias, Gene Regulatory Networks, Host Microbial Interactions genetics, Host Microbial Interactions physiology, Humans, Influenza A virus drug effects, Lipopolysaccharides pharmacology, Macrophages, RNA Caps genetics, RNA, Messenger, RNA, Small Nuclear metabolism, RNA, Viral genetics, RNA-Dependent RNA Polymerase genetics, Virus Replication, Base Sequence, Influenza A virus genetics, Influenza, Human virology, Transcription, Genetic physiology
Abstract

Macrophages in the lung detect and respond to influenza A virus (IAV), determining the nature of the immune response. Using terminal-depth cap analysis of gene expression (CAGE), we quantified transcriptional activity of both host and pathogen over a 24-h time course of IAV infection in primary human monocyte-derived macrophages (MDMs). This method allowed us to observe heterogenous host sequences incorporated into IAV mRNA, "snatched" 5' RNA caps, and corresponding RNA sequences from host RNAs. In order to determine whether cap-snatching is random or exhibits a bias, we systematically compared host sequences incorporated into viral mRNA ("snatched") against a complete survey of all background host RNA in the same cells, at the same time. Using a computational strategy designed to eliminate sources of bias due to read length, sequencing depth, and multimapping, we were able to quantify overrepresentation of host RNA features among the sequences that were snatched by IAV. We demonstrate biased snatching of numerous host RNAs, particularly small nuclear RNAs (snRNAs), and avoidance of host transcripts encoding host ribosomal proteins, which are required by IAV for replication. We then used a systems approach to describe the transcriptional landscape of the host response to IAV, observing many new features, including a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation, seen in response to other treatments. IMPORTANCE Infection with influenza A virus (IAV) infection is responsible for an estimated 500,000 deaths and up to 5 million cases of severe respiratory illness each year. In this study, we looked at human primary immune cells (macrophages) infected with IAV. Our method allows us to look at both the host and the virus in parallel. We used these data to explore a process known as "cap-snatching," where IAV snatches a short nucleotide sequence from capped host RNA. This process was believed to be random. We demonstrate biased snatching of numerous host RNAs, including those associated with snRNA transcription, and avoidance of host transcripts encoding host ribosomal proteins, which are required by IAV for replication. We then describe the transcriptional landscape of the host response to IAV, observing new features, including a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation, seen in response to other treatments., (Copyright © 2020 Clohisey et al.)

Published
2020
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21. 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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