Suzuki Harukazu, Forrest Alistair R R, van Nimwegen Erik, Daub Carsten O, Balwierz Piotr J, Irvine Katharine M, Lassmann Timo, Ravasi Timothy, Hasegawa Yuki, de Hoon Michiel J L, Katayama Shintaro, Schroder Kate, Carninci Piero, Tomaru Yasuhiro, Kanamori-Katayama Mutsumi, Kubosaki Atsutaka, Akalin Altuna, Ando Yoshinari, Arner Erik, Asada Maki, Asahara Hiroshi, Bailey Timothy, Bajic Vladimir B, Bauer Denis, Beckhouse Anthony G, Bertin Nicolas, Björkegren Johan, Brombacher Frank, Bulger Erika, Chalk Alistair M, Chiba Joe, Cloonan Nicole, Dawe Adam, Dostie Josee, Engström Pär G, Essack Magbubah, Faulkner Geoffrey J, Fink J Lynn, Fredman David, Fujimori Ko, Furuno Masaaki, Gojobori Takashi, Gough Julian, Grimmond Sean M, Gustafsson Mika, Hashimoto Megumi, Hashimoto Takehiro, Hatakeyama Mariko, Heinzel Susanne, Hide Winston, Hofmann Oliver, Hörnquist Michael, Huminiecki Lukasz, Ikeo Kazuho, Imamoto Naoko, Inoue Satoshi, Inoue Yusuke, Ishihara Ryoko, Iwayanagi Takao, Jacobsen Anders, Kaur Mandeep, Kawaji Hideya, Kerr Markus C, Kimura Ryuichiro, Kimura Syuhei, Kimura Yasumasa, Kitano Hiroaki, Koga Hisashi, Kojima Toshio, Kondo Shinji, Konno Takeshi, Krogh Anders, Kruger Adele, Kumar Ajit, Lenhard Boris, Lennartsson Andreas, Lindow Morten, Lizio Marina, Macpherson Cameron, Maeda Norihiro, Maher Christopher A, Maqungo Monique, Mar Jessica, Matigian Nicholas A, Matsuda Hideo, Mattick John S, Meier Stuart, Miyamoto Sei, Miyamoto-Sato Etsuko, Nakabayashi Kazuhiko, Nakachi Yutaka, Nakano Mika, Nygaard Sanne, Okayama Toshitsugu, Okazaki Yasushi, Okuda-Yabukami Haruka, Orlando Valerio, Otomo Jun, Pachkov Mikhail, Petrovsky Nikolai, Plessy Charles, Quackenbush John, Radovanovic Aleksandar, Rehli Michael, Saito Rintaro, Sandelin Albin, Schmeier Sebastian, Schönbach Christian, Schwartz Ariel S, Semple Colin A, Sera Miho, Severin Jessica, Shirahige Katsuhiko, Simons Cas, St Laurent George, Suzuki Masanori, Suzuki Takahiro, Sweet Matthew J, Taft Ryan J, Takeda Shizu, Takenaka Yoichi, Tan Kai, Taylor Martin S, Teasdale Rohan D, Tegnér Jesper, Teichmann Sarah, Valen Eivind, Wahlestedt Claes, Waki Kazunori, Waterhouse Andrew, Wells Christine A, Winther Ole, Wu Linda, Yamaguchi Kazumi, Yanagawa Hiroshi, Yasuda Jun, Zavolan Mihaela, Hume David A, Arakawa Takahiro, Fukuda Shiro, Imamura Kengo, Kai Chikatoshi, Kaiho Ai, Kawashima Tsugumi, Kawazu Chika, Kitazume Yayoi, Kojima Miki, Miura Hisashi, Murakami Kayoko, Murata Mitsuyoshi, Ninomiya Noriko, Nishiyori Hiromi, Noma Shohei, Ogawa Chihiro, Sano Takuma, Simon Christophe, Tagami Michihira, Takahashi Yukari, Kawai Jun, Hayashizaki Yoshihide
RIKEN Omics Science Center, RIKEN Yokohama Institute, Kanagawa, Japan.
Nat Genet. 2009 May;41(5):553-62. doi: 10.1038/ng.375. Epub 2009 Apr 19.
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.
利用深度测序（deepCAGE），FANTOM4研究在人单核细胞系THP-1生长停滞和分化的时间进程中，测量了全基因组转录起始位点使用的动态变化。通过预测的顺式调控位点对表达动态进行建模，我们确定了关键转录调节因子、它们的时间依赖性活性和靶基因。对52种转录因子进行系统性小干扰RNA敲低，证实了各个因子在调控网络中的作用。我们的结果表明，细胞状态受到复杂网络的限制，这些网络涉及大量转录因子之间的正负调控相互作用，而且没有单个转录因子对于驱动分化过程既是必需的又是充分的。
