Unprogrammed epigenetic variation mediated by stochastic formation of ectopic heterochromatin

Curr Genet. 2020 Apr;66(2):319-325. doi: 10.1007/s00294-019-01031-4. Epub 2019 Oct 9.

Abstract

Changes in gene expression via chromatin-mediated mechanisms are important for reprogramming and differentiation, but uncontrolled changes can potentially lead to harmful or adaptive phenotypic alteration. Thus, diversification of the genome-wide chromatin state must be strictly limited, but the underlying mechanism of this regulation is largely unknown. In this review, we focused on distribution of heterochromatin, a tight chromatin structure that negatively regulates gene expression. Heterochromatin is characterized by methylation of histone H3 at lysine 9, and its formation and spreading are controlled by H3K9-specific methyltransferases and reversal factors such as histone demethylases. We summarize recent findings and discuss how variability in the heterochromatin distribution is controlled in the unicellular eukaryote fission yeast. In this context, we recently found that the anti-silencing factor Epe1 plays a key role in the formation of the individual-specific heterochromatin distribution. In conclusion, recent studies revealed that there are many potential heterochromatin formation sites in the fission yeast genome, and several proteins contribute to suppression of spreading and genome-wide dispersal of heterochromatin; knowledge from fission yeast studies may provide insights into the mechanisms regulating epigenetic diversification in multicellular eukaryotes.

Keywords: Ectopic heterochromatin; Epe1; Epigenetic variation; Fission yeast; H3K9 methylation; JmjC.

Publication types

  • Review

MeSH terms

  • Chromatin Assembly and Disassembly
  • Epigenesis, Genetic*
  • Heterochromatin / metabolism*
  • Histones / metabolism*
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Methylation
  • Methyltransferases / metabolism
  • Protein Processing, Post-Translational
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism

Substances

  • Heterochromatin
  • Histones
  • Jumonji Domain-Containing Histone Demethylases
  • Methyltransferases