The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line
Nature Genetics2009Vol. 41(5), pp. 553–562
Citations Over TimeTop 1% of 2009 papers
Hideya Kawaji, Norihiro Maeda, Takehiro Hashimoto, Kayoko Murakami, Andreas Lennartsson, Timo Lassmann, Kazumi Yamaguchi, Shohei Noma, Yayoi Kitazume, Noriko Ninomiya, Yasuhiro Tomaru, Ryoko Ishihara, Chika Kawazu, Shiro Fukuda, Nicolas Bertin, Takahiro Suzuki, Mika Nakano, Chikatoshi Kai, Tsugumi Kawashima, Y. Hayashizaki, Chihiro Ogawa, Yuki Hasegawa, Carsten O. Daub, Jessica Severin, Takuma Sano, Kazunori Waki, Mutsumi Kanamori-Katayama, Harukazu Suzuki, Alistair R R Forrest, Shintaro Katayama, Yukari Takahashi, Hiromi Nishiyori, Masaaki Furuno, Andrew Waterhouse, Haruka Okuda-Yabukami, Miki Kojima, Charles Plessy, Erika Bulger, Erik Arner, Shinji Kondo, Mitsuyoshi Murata, Michihira Tagami, Michiel de Hoon, Yoshinari Ando, Jun Yasuda, Hisashi Miura, Atsutaka Kubosaki, Piero Carninci, Christophe Simon, Jun Kawai, Kengo Imamura, Masanori Suzuki, Takahiro Arakawa, Yasumasa Kimura, Marina Lizio, Ai Kaiho, Christine A. Wells, Alistair M. Chalk, Anthony G Beckhouse, Alistair R R Forrest, Nicholas Matigian, Piotr J. Balwierz, Mihaela Zavolan, Erik van Nimwegen, Mikhail Pachkov, Katharine M. Irvine, Kate Schroder, Timothy L. Bailey, Denis C. Bauer, Timothy Ravasi, Ariel Schwartz, Kai Tan, Altuna Akalin, Pär G. Engström, Boris Lenhard, David Fredman, Megumi Hashimoto, Maki Asada, Hiroshi Asahara, Magbubah Essack, Adam Dawe, Vladimir B. Bajić, Adéle Kruger, Aleksandar Radovanović, Mandeep Kaur, Cameron Ross MacPherson, Monique Maqungo, Christopher A. Maher, Winston Hide, Oliver Hofmann, Stuart Meier, Sebastian Schmeier, Johan Björkegren, Jesper Tegnér, Frank Brombacher, Joe Chiba, Kazuhiko Nakabayashi, Ryuichiro Kimura, Ryan J. Taft, Sean M. Grimmond, John S. Mattick, Geoffrey J. Faulkner, Cas Simons, Nicole Cloonan, Josée Dostie, J. Lynn Fink, Markus C. Kerr, Rohan D. Teasdale, Ko Fujimori, T. Konno, Takashi Gojobori, Toshitsugu Okayama, Sei Miyamoto, Miho Sera, Kazuho Ikeo, Julian Gough, Michael Hörnquist, Mika Gustafsson, Mariko Hatakeyama, Toshio Kojima, Linda Wu, Susanne Heinzel, Nikolai Petrovsky, Oliver Hofmann, Winston Hide , Łukasz Huminiecki, Naoko Imamoto, Satoshi Inoue, Yusuke Inoue, Takao Iwayanagi, Albin Sandelin, Ole Winther, Anders J. Skanderup, Sanne Nygaard, Anders Krogh, Eivind Valen, Morten Lindow, Syuhei Kimura, Hiroaki Kitano, Hisashi Koga, George St. Laurent, Ajit Kumar, Jessica C. Mar, John Quackenbush, Yoichi Takenaka, Hideo Matsuda, Hiroshi Yanagawa, Etsuko Miyamoto‐Sato, Yutaka Nakachi, Yasushi Okazaki, Valerio Orlando, Jun Otomo, Shizu Takeda, Michael Rehli, Rintaro Saito, Christian Schönbach, Colin A. Semple, Katsuhiko Shirahige, Matthew J. Sweet, Martin S. Taylor, Jesper Tegnér, Sarah A. Teichmann, Claes Wahlestedt, David Hume
Abstract
Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.
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