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Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

2015; American Association for the Advancement of Science; Volume: 347; Issue: 6225 Linguagem: Inglês

10.1126/science.1259418

1095-9203

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

RNA and protein synthesis mechanisms

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.