An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man

Ravasi, Timothy; Suzuki, Harukazu; Cannistraci, Carlo; Katayama, Shintaro; Bajic, Vladimir B.; Tan, Kai; Akalin, Altuna; Schmeier, Sebastian; Kanamori-Katayama, Mutsumi; Bertin, Nicolas; Carninci, Piero; Daub, Carsten O.; Forrest, Alistair R.R.; Gough, Julian; Grimmond, Sean; Han, Jung-Hoon; Hashimoto, Takehiro; Hide, Winston; Hofmann, Oliver; Kamburov, Atanas; Kaur, Mandeep; Kawaji, Hideya; Kubosaki, Atsutaka; Lassmann, Timo; van Nimwegen, Erik; MacPherson, Cameron Ross; Ogawa, Chihiro; Radovanovic, Aleksandar; Schwartz, Ariel; Teasdale, Rohan D.; Tegnér, Jesper; Lenhard, Boris; Teichmann, Sarah A.; Arakawa, Takahiro; Ninomiya, Noriko; Murakami, Kayoko; Tagami, Michihira; Fukuda, Shiro; Imamura, Kengo; Kai, Chikatoshi; Ishihara, Ryoko; Kitazume, Yayoi; Kawai, Jun; Hume, David A.; Ideker, Trey; Hayashizaki, Yoshihide

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KAUST Department

Biological and Environmental Sciences and Engineering (BESE) Division
Bioscience Program
Computational Bioscience Research Center (CBRC)
Bioscience Program
Integrative Systems Biology Lab
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Applied Mathematics and Computational Science Program
Computational Bioscience Research Center (CBRC)
Applied Mathematics and Computational Science Program

Date

2010-03-05

Embargo End Date

2011-03-05

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http://hdl.handle.net/10754/575669

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Abstract

Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

Sponsors

The work for the RIKEN Omics Science Center was supported by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) through the Genome Network Project and for the RIKEN Omics Science Center (YH, Principal Investigator). Members of the FANTOM Consortium were supported by grant MH062261 from the US National Institute of Mental Health (TR, KT, TI), the King Abdullah University of Science and Technology (TR, VBB), the Max Planck Society for the Advancement of Science (AK), the SA National Bioinformatics Network (SS, AR, VBB, WAH), the Claude Leon Foundation (MK), a CJ Martin Fellowship from the Australian NHMRC (ARRF), and the Scuola Interpolitecnica di Dottorato (CVC). The authors gratefully acknowledge S. Choi for critical feedback on the manuscript.