Occupancy of tissue-specific cis-regulatory modules by Otx2 and TLE/Groucho for embryonic head specification

Yuuri Yasuoka, Yutaka Suzuki, Shuji Takahashi, Haruka Someya, Norihiro Sudou, Yoshikazu Haramoto, Ken W. Cho, Makoto Asashima, Sumio Sugano and Masanori Taira ()
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Yuuri Yasuoka: Graduate School of Science, University of Tokyo
Yutaka Suzuki: Graduate School of Frontier Sciences, University of Tokyo
Shuji Takahashi: Komaba Organization for Educational Excellence, College of Arts and Sciences, University of Tokyo
Haruka Someya: Graduate School of Science and Engineering, Tokyo Metropolitan University
Norihiro Sudou: Graduate School of Science, University of Tokyo
Yoshikazu Haramoto: Komaba Organization for Educational Excellence, College of Arts and Sciences, University of Tokyo
Ken W. Cho: Developmental Biology Center, University of California
Makoto Asashima: Research Center for Stem Cell Engineering (SCRC), National Institute of Advanced Industrial Science and Technology (AIST)
Sumio Sugano: Graduate School of Frontier Sciences, University of Tokyo
Masanori Taira: Graduate School of Science, University of Tokyo

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract Head specification by the head-selector gene, orthodenticle (otx), is highly conserved among bilaterian lineages. However, the molecular mechanisms by which Otx and other transcription factors (TFs) interact with the genome to direct head formation are largely unknown. Here we employ ChIP-seq and RNA-seq approaches in Xenopus tropicalis gastrulae and find that occupancy of the corepressor, TLE/Groucho, is a better indicator of tissue-specific cis-regulatory modules (CRMs) than the coactivator p300, during early embryonic stages. On the basis of TLE binding and comprehensive CRM profiling, we define two distinct types of Otx2- and TLE-occupied CRMs. Using these devices, Otx2 and other head organizer TFs (for example, Lim1/Lhx1 (activator) or Goosecoid (repressor)) are able to upregulate or downregulate a large battery of target genes in the head organizer. An underlying principle is that Otx marks target genes for head specification to be regulated positively or negatively by partner TFs through specific types of CRMs.

Date: 2014
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DOI: 10.1038/ncomms5322

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