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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.

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Author

  • Chengdong Wang
  • Richard Kin Ting Kam
  • Weili Shi
  • Yin Xia
  • Xiongfong Chen
  • Ying Cao
  • Jianmin Sun
  • Yanzhi Du
  • Gang Lu
  • Zijiang Chen
  • Wood Yee Chan
  • Sun On Chan
  • Yi Deng
  • Hui Zhao
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Summary, in English

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-neuralectoderm 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 (HDAC1), suggesting that Ets1 recruits HDAC1 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.

Publishing year

2015

Language

English

Pages

21925-21938

Publication/Series

Journal of Biological Chemistry

Volume

290

Issue

36

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1083-351X