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J Biol Chem 2015 Sep 04;29036:21925-38. doi: 10.1074/jbc.M115.644864.
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The Proto-oncogene Transcription Factor Ets1 Regulates Neural Crest Development through Histone Deacetylase 1 to Mediate Output of Bone Morphogenetic Protein Signaling.

Wang C , Kam RK , Shi W , Xia Y , Chen X , Cao Y , Sun J , Du Y , Lu G , Chen Z , Chan WY , Chan SO , Deng Y , Zhao H .

The neural crest (NC) is a transient, migratory cell population that differentiates into a large variety of tissues including craniofacial cartilage, melanocytes, and peripheral nervous system. NC is initially induced at the border of neural plate and non-neural ectoderm by balanced regulation of multiple signaling pathways among which an intermediate bone morphogenetic protein (BMP) signaling is essential for NC formation. ets1, a proto-oncogene playing important roles in tumor invasion, has also been implicated in delamination of NC cells. In this study, we investigated Ets1 function in NC formation using Xenopus. Overexpression of ets1 repressed NC formation through down-regulation of BMP signaling. Moreover, ets1 repressed the BMP-responsive gene id3 that is essential for NC formation. Conversely, overexpression of id3 can partially rescue the phenotype of NC inhibition induced by ectopic ets1. Mechanistically, we found that Ets1 binds to id3 promoter as well as histone deacetylase 1, suggesting that Ets1 recruits histone deacetylase 1 to the promoter of id3, thereby inducing histone deacetylation of the id3 promoter. Thus, our studies indicate that Ets1 regulates NC formation through attenuating BMP signaling epigenetically.

PubMed ID: 26198637
PMC ID: PMC4571947
Article link: J Biol Chem

Species referenced: Xenopus laevis
Genes referenced: bmp4 chrd ets1 ets2 etv2 fgf4 foxd3 hdac1 hes4 id3 krt12.4 lrig3 msx1 myc ncam1 pax3 smad1 snai2 sncg sox2 sox3 szl tbxt twist1 wnt3a zic1
Morpholinos: ets1 MO1 ets1 MO2 ets1 MO3

GEO Series: GSE50487: NCBI
Phenotypes: Xla Wt + TSA (Fig.7.M) [+]

Article Images: [+] show captions
References [+] :
Akkers, Chromatin immunoprecipitation analysis of Xenopus embryos. 2012, Pubmed, Xenbase