G9a, a multipotent regulator of gene expression

Epigenetics. 2013 Jan;8(1):16-22. doi: 10.4161/epi.23331. Epub 2012 Dec 20.


Lysine methylation of histone and non-histone substrates by the methyltransferase G9a is mostly associated with transcriptional repression. Recent studies, however, have highlighted its role as an activator of gene expression through mechanisms that are independent of its methyltransferase activity. Here we review the growing repertoire of molecular mechanisms and substrates through which G9a regulates gene expression. We also discuss emerging evidence for its wide-ranging functions in development, pluripotency, cellular differentiation and cell cycle regulation that underscore the complexity of its functions. The deregulated expression of G9a in cancers and other human pathologies suggests that it may be a viable therapeutic target in various diseases.

Keywords: cancer; chromatin modifier; differentiation; gene expression; histones; methylation; transcription; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cellular Senescence
  • Gene Expression Regulation*
  • Histone-Lysine N-Methyltransferase / chemistry
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Humans
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Repressor Proteins / metabolism
  • Trans-Activators / metabolism


  • Repressor Proteins
  • Trans-Activators
  • Histone-Lysine N-Methyltransferase