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

Authors
Harukazu Suzuki,Alistair Forrest
Erik Nimwegen,Carsten Daub,Piotr Balwierz,Katharine Irvine,Timo Lassmann,Timothy Ravasi,Yuki Hasegawa,Michiel Hoon,Shintaro Katayama,Kate Schroder,Piero Carninci,Yuji Tomaru,Mutsumi Kanamori-Katayama,Atsutaka Kubosaki,Altuna Akalin,Yoshinari Ando,Erik Arner,Maki Asada,Hiroshi Asahara,Timothy Bailey,Vladimir Bajić,Douglas Bauer,Anthony Beckhouse,Nicolas Bertin,Johan Björkegren,Frank Brombacher,Eileen Bulger,Alistair Chalk,Joe Chiba,Nicole Cloonan,Adam Dawe,Josée Dostie,Pär Engström,Magbubah Essack,Geoffrey Faulkner,J. Fink,David Fredman,Ko Fujimori,Masaaki Furuno,Takashi Gojobori,Julian Gough,Sean Grimmond,Mika Gustafsson,Megumi Hashimoto,Takehiro Hashimoto,Mariko Okada,Susanne Heinzel,Winston Hide,Oliver Hofmann,Michael Hörnquist,Łukasz Huminiecki,Kazuho Ikeo,Naoko Imamoto,Satoshi Inoue,Yusuke Inoue,Ryoko Ishihara,Takao Iwayanagi,Anders Skanderup,Mandeep Kaur,Hideya Kawaji,Markus Kerr,Ryuichiro Kimura,Syuhei Kimura,Yasumasa Kimura,Hiroaki Kitano,Hisashi Koga,Toshio Kojima,Shinji Kondo,Tasuke Konno,Anders Krogh,Adéle Kruger,Ajit Kumar,Boris Lenhard,Andreas Lennartsson,Morten Lindow,Marina Lizio,Cameron MacPherson,Norihiro Maeda,Christopher Maher,Monique Maqungo,Jessica Mar,Nicholas Matigian,Hideo Matsuda,John Mattick,Stuart Meier,Sei Miyamoto,Etsuko Miyamoto‐Sato,Kazuhiko Nakabayashi,Yutaka Nakachi,Masuo 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,Masayoshi Itoh,Albin Sandelin,Sebastian Schmeier,Christian Schönbach,Ariel Schwartz,Colin Semple,Miho Sera,Jessica Severin,Katsuhiko Shirahige,Cas Simons,G Laurent,Masanori Suzuki,Takahiro Suzuki,Matthew Sweet,Ryan Taft,Shizu Takeda,Yoichi Takenaka,Kai Tan,Martin Taylor,Rohan Teasdale,Jesper Tegnér,Sarah Teichmann,Eivind Valen,Claes Wahlestedt,Kazunori Waki,Andrew Waterhouse,Christine 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-Sueki,Shohei Noma,Chihiro Ogawa,Takuma Sano,Christophe Simon,Michihira Tagami,Yukari Tanikawa,Jun Kawai,Y. Hayashizaki,Yasuhiro Tomaru,Vladimir Bajic,Denis Bauer,Erika Bulger,Mariko Hatakeyama
+163 authors
,Mika Nakano
Published
Apr 19, 2009
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Abstract

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.

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