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Nat Commun 2014 Jul 09;5:4322. doi: 10.1038/ncomms5322.
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Occupancy of tissue-specific cis-regulatory modules by Otx2 and TLE/Groucho for embryonic head specification.

Yasuoka Y , Suzuki Y , Takahashi S , Someya H , Sudou N , Haramoto Y , Cho KW , Asashima M , Sugano S , Taira M .

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.

PubMed ID: 25005894
PMC ID: PMC4805429
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: acta1 actc1 admp bmp4 cer1 chrd crebbp crx cyp26a1 dkk1 en2 eomes ezh2 fgf8 foxa4 foxb1 foxd4l1.1 frzb frzb2 fzd8 gsc jarid2 ldb1 lhx1 meis1 meis3 nog not otx2 pbx1 prdm1 ssbp3 tbxt tle1 tle2 tle4 vegt ventx1 ventx2.2 wnt11 wnt8a
GO keywords: body morphogenesis [+]
Antibodies: Acetylated H3f3a Ab20 Tle1 Ab1 ep300 Ab1 methyl-H3f3a Ab13
Morpholinos: crx MO1 gsc MO1 lhx1 MO4 otx2 MO1

GEO Series: GSE172076: NCBI
Phenotypes: Xla Wt + gsc + ssbp3 + tle1 + lhx1 mRNA 5 (Fig. S3 A) [+]

Article Images: [+] show captions
References [+] :
Acampora, Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation. 1995, Pubmed