Occupancy of Tissue-Specific Cis-Regulatory Modules by Otx2 and TLE/Groucho for Embryonic Head Specification

Nat Commun. 2014 Jul 9;5:4322. doi: 10.1038/ncomms5322.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Binding Sites
  • Female
  • Gastrula / embryology
  • Gastrula / metabolism
  • Gene Expression Regulation, Developmental*
  • Head / embryology*
  • Male
  • Organ Specificity
  • Otx Transcription Factors / genetics
  • Otx Transcription Factors / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Xenopus / embryology
  • Xenopus / genetics
  • Xenopus / metabolism*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Otx Transcription Factors
  • Otx2 protein, Xenopus
  • TLE1 protein, Xenopus
  • Transcription Factors
  • Xenopus Proteins

Associated data

  • SRA/DRA000505
  • SRA/DRA000506
  • SRA/DRA000507
  • SRA/DRA000508
  • SRA/DRA000509
  • SRA/DRA000510
  • SRA/DRA000514
  • SRA/DRA000515
  • SRA/DRA000516
  • SRA/DRA000517
  • SRA/DRA000518
  • SRA/DRA000573
  • SRA/DRA000574
  • SRA/DRA000575
  • SRA/DRA000576
  • SRA/DRA000577
  • SRA/DRA000642
  • SRA/DRA000645
  • SRA/DRA000648
  • SRA/DRA000649
  • SRA/DRA000732
  • SRA/DRA001093
  • SRA/DRA001094
  • SRA/DRA001095