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

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 J.L. De Hoon, Shintaro Katayama, Kate Schroder, Piero Carninci, Yasuhiro Tomaru, Mutsumi Kanamori-Katayama, Atsutaka Kubosaki, Altuna Akalin, Yoshinari Ando, Erik Arner, Maki AsadaHiroshi Asahara, Timothy Bailey, Vladimir B. Bajic, Denis Bauer, Anthony G. Beckhouse, Nicolas Bertin, Johan Björkegren, Frank Brombacher, Erika Bulger, Alistair M. Chalk, Joe Chiba, Nicole Cloonan, Adam Dawe, Josee 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, Winston Hide, Oliver Hofmann, Michael Hörnquist, Lukasz Huminiecki, Kazuho Ikeo, Naoko Imamoto, Satoshi Inoue, Yusuke Inoue, Ryoko Ishihara, Takao Iwayanagi, Anders Jacobsen, Mandeep Kaur, Hideya Kawaji, Markus C. Kerr, Ryuichiro Kimura, Syuhei Kimura, Yasumasa Kimura, Hiroaki Kitano, Hisashi Koga, Toshio Kojima, Shinji Kondo, Takeshi Konno, Anders Krogh, Adele Kruger, Ajit Kumar, Boris Lenhard, Andreas Lennartsson, Morten Lindow, Marina Lizio, Cameron MacPherson, Norihiro Maeda, Christopher A. Maher, Monique Maqungo, Jessica Mar, Nicholas A. 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 Radovanovic, Michael Rehli, Rintaro Saito, Albin Sandelin, Sebastian Schmeier, Christian Schönbach, Ariel S. 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 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 A. 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, Yoshihide Hayashizaki

Research output: Contribution to journalArticle

313 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)553-562
Number of pages10
JournalNature genetics
Volume41
Issue number5
DOIs
StatePublished - May 2009

ASJC Scopus subject areas

  • Genetics

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    Suzuki, H., Forrest, A. R. R., Van Nimwegen, E., Daub, C. O., Balwierz, P. J., Irvine, K. M., Lassmann, T., Ravasi, T., Hasegawa, Y., De Hoon, M. J. L., Katayama, S., Schroder, K., Carninci, P., Tomaru, Y., Kanamori-Katayama, M., Kubosaki, A., Akalin, A., Ando, Y., Arner, E., ... Hayashizaki, Y. (2009). The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nature genetics, 41(5), 553-562. https://doi.org/10.1038/ng.375