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The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

2009; Nature Portfolio; Volume: 41; Issue: 5 Linguagem: Inglês

10.1038/ng.375

1546-1718

Harukazu Suzuki, Alistair R. R. Forrest, Erik van Nimwegen, Carsten O. Daub, Piotr J. Balwierz, Katharine M. Irvine, Timo Lassmann, Timothy Ravasi, Yuki Hasegawa, Michiel de Hoon, Shintaro Katayama, Kate Schroder, Piero Carninci, Yasuhiro Tomaru, Mutsumi Kanamori-Katayama, Atsutaka Kubosaki, Altuna Akalin, Yoshinari Ando, Erik Arner, Maki Asada, Hiroshi Asahara, Timothy L. Bailey, Vladimir B. Bajić, Denis C. Bauer, Anthony G Beckhouse, Nicolas Bertin, Johan Björkegren, Frank Brombacher, Erika Bulger, Alistair M. Chalk, Joe Chiba, Nicole Cloonan, Adam Dawe, Josée Dostie, Pär G. Engström, Magbubah Essack, Geoffrey J. Faulkner, J. Lynn Fink, David Fredman, Ko Fujimori, Masaaki Furuno, Takashi Gojobori, Julian Gough, Sean M. Grimmond, Mika Gustafsson, Megumi Hashimoto, Takehiro Hashimoto, Mariko Hatakeyama, Susanne Heinzel, Yoshihide Hayashizaki, Oliver Hofmann, Michael Hörnquist, Łukasz Huminiecki, Kazuho Ikeo, Naoko Imamoto, Satoshi Inoue, Yusuke Inoue, Ryoko Ishihara, Takao Iwayanagi, Anders J. Skanderup, Mandeep Kaur, Hideya Kawaji, Markus C. Kerr, Ryuichiro Kimura, Syuhei Kimura, Yasumasa Kimura, Hiroaki Kitano, Hisashi Koga, Toshio Kojima, Shinji Kondo, T. Konno, Anders Krogh, Adéle Kruger, Ajit Kumar, Boris Lenhard, Andreas Lennartsson, Morten Lindow, Marina Lizio, Cameron Ross MacPherson, Norihiro Maeda, Christopher A. Maher, Monique Maqungo, Jessica C. Mar, Nicholas Matigian, Hideo Matsuda, John S. Mattick, Stuart Meier, Sei Miyamoto, Etsuko Miyamoto‐Sato, Kazuhiko Nakabayashi, Yutaka Nakachi, Mika Nakano, Sanne Nygaard, Toshitsugu Okayama, Yasushi Okazaki, Haruka Okuda-Yabukami, Valerio Orlando, Jun Otomo, Mikhail Pachkov, Nikolai Petrovsky, Charles Plessy, John Quackenbush, Aleksandar Radovanović, Michael Rehli, Rintaro Saito, Albin Sandelin, Sebastian Schmeier, Christian Schönbach, Ariel Schwartz, Colin A. Semple, Miho Sera, Jessica Severin, Katsuhiko Shirahige, Cas Simons, George St. Laurent, Masanori Suzuki, Takahiro Suzuki, Matthew J. Sweet, Ryan J. Taft, Shizu Takeda, Yoichi Takenaka, Kai Tan, Martin S. Taylor, Rohan D. Teasdale, Jesper Tegnér, Sarah A. Teichmann, Eivind Valen, Claes Wahlestedt, Kazunori Waki, Andrew Waterhouse, Christine A. Wells, Ole Winther, Linda Wu, Kazumi Yamaguchi, Hiroshi Yanagawa, Jun Yasuda, Mihaela Zavolan, David Hume, Takahiro Arakawa, Shiro Fukuda, Kengo Imamura, Chikatoshi Kai, Ai Kaiho, Tsugumi Kawashima, Chika Kawazu, Yayoi Kitazume, Miki Kojima, Hisashi Miura, Kayoko Murakami, Mitsuyoshi Murata, Noriko Ninomiya, Hiromi Nishiyori, Shohei Noma, Chihiro Ogawa, Takuma Sano, Christophe Simon, Michihira Tagami, Yukari Takahashi, Jun Kawai, Y. Hayashizaki,

RNA Research and Splicing

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process. Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.