Histone demethylase Kdm2a regulates germ cell genes and endogenous retroviruses in embryonic stem cells

Epigenomics. 2019 May;11(7):751-766. doi: 10.2217/epi-2018-0126. Epub 2019 Jun 7.

Abstract

Aim: To investigate the function of Kdm2a in embryonic stem cells (ESCs). Materials & methods: Expression profile analysis after Kdm2a knockout. Analysis of Kdm2a, H3K4me3 and H3K27me3 ChIP-seq data in ESCs. qPCR analysis and ChIP-qPCR analysis of epigenetic changes after Kdm2a loss. Results:Kdm2a was dispensable for pluripotency maintenance in ESCs. Kdm2a genomic binding profile was positively correlated with that of H3K4me3, Zfx and Tet1. Kdm2a directly regulated germ cell genes in primordial germ cell-like cells. Kdm2a loss led to the reduced expression of endogenous retrovirus IAPEy and resulted in the gain of H3K36me2 and loss of H3K4me3 on IAPEy. Conclusion: Kdm2a regulates germ cell genes and endogenous retroviruses in ESCs possibly through demethylating H3K36me2 and influencing H3K4me3 deposition.

Keywords: embryonic stem cell; endogenous retrovirus; histone demethylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Embryoid Bodies / pathology
  • Endogenous Retroviruses / physiology*
  • Gene Expression Regulation
  • Histones / metabolism
  • Jumonji Domain-Containing Histone Demethylases / deficiency
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Mouse Embryonic Stem Cells / virology
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • Histones
  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins
  • TET1 protein, mouse
  • histone H3 trimethyl Lys4
  • zinc finger protein, X-linked
  • FBXL11 protein, mouse
  • Jumonji Domain-Containing Histone Demethylases