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Nat Commun July 9, 2014; 5 4322.

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: [+]
Genes referenced: acta1 actc1 admp bmp4 cer1 chrd.1 crebbp crx cyp26a1 dkk1 en2 eomes ep300 ezh2 fgf8 foxa4 foxb1 foxd4l1.1 frzb frzb2 fzd8 gsc jarid2 ldb1 lhx1 meis1 meis3 mmut nog not otx2 pbx1 prdm1 ssbp3 tbxt tle1 tle2 tle4 vegt ventx1.1 ventx2.2 wnt11 wnt8a
Morpholinos: gsc MO1

Article Images: [+] show captions
Acampora, 1995, Pubmed [+]

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