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Stem cell-like Xenopus Embryonic Explants to Study Early Neural Developmental Features In Vitro and In Vivo
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Lsh controls Hox gene silencing during development.

Sichuan Xi1, Heming Zhu, Hong Xu

  • 1Laboratory of Cancer Prevention, SAIC-Frederick, National Cancer Institute, Frederick, MD 21702-1201, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 30, 2007
PubMed
Summary

Lsh, a DNA methylation regulator, controls Polycomb Repressive Complex (PRC) silencing of Hox genes during development. It forms a feedback loop reinforcing DNA methylation and gene silencing.

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Area of Science:

  • Epigenetics
  • Developmental Biology
  • Gene Regulation

Background:

  • Polycomb-mediated repression and DNA methylation are key epigenetic gene silencing mechanisms.
  • A link between Polycomb Repressive Complex (PRC) and DNA methyltransferases (Dnmts) is suggested in cancer.
  • The role of Lsh in normal embryonic gene silencing is not well understood.

Purpose of the Study:

  • To investigate the role of Lsh in Polycomb-mediated gene silencing during embryogenesis.
  • To determine if Lsh interacts with PRC components and influences DNA methylation.
  • To elucidate the physiological feedback loop involving Lsh, DNA methylation, and PRC targets.

Main Methods:

  • Chromatin immunoprecipitation assays to assess Lsh and PRC1 binding to Hox genes.
  • DNA methylation analysis of Hox gene loci.
  • Assessment of histone modifications associated with PRC-mediated silencing.

Main Results:

  • Lsh associates with specific Hox genes during development.
  • Lsh regulates the binding of Dnmt3b, DNA methylation, and silencing of Hox genes.
  • Lsh interacts with PRC1 components and influences PRC-mediated histone modifications.
  • Lsh participates in a feedback loop that strengthens DNA methylation and silencing of PRC targets.

Conclusions:

  • Lsh is a crucial regulator of PRC-mediated gene silencing in normal development.
  • Lsh integrates DNA methylation and Polycomb repression pathways.
  • Lsh plays a role in a feedback mechanism that ensures stable epigenetic silencing.