Evolutionarily ancient BAH-PHD protein mediates Polycomb silencing

Proc Natl Acad Sci U S A. 2020 May 26;117(21):11614-11623. doi: 10.1073/pnas.1918776117. Epub 2020 May 11.

Abstract

Methylation of histone H3 lysine 27 (H3K27) is widely recognized as a transcriptionally repressive chromatin modification but the mechanism of repression remains unclear. We devised and implemented a forward genetic scheme to identify factors required for H3K27 methylation-mediated silencing in the filamentous fungus Neurospora crassa and identified a bromo-adjacent homology (BAH)-plant homeodomain (PHD)-containing protein, EPR-1 (effector of polycomb repression 1; NCU07505). EPR-1 associates with H3K27-methylated chromatin, and loss of EPR-1 de-represses H3K27-methylated genes without loss of H3K27 methylation. EPR-1 is not fungal-specific; orthologs of EPR-1 are present in a diverse array of eukaryotic lineages, suggesting an ancestral EPR-1 was a component of a primitive Polycomb repression pathway.

Keywords: H3K27 methylation; Polycomb repressive complex; epigenetics; facultative heterochromatin; histone reader.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epigenesis, Genetic / genetics
  • Evolution, Molecular*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Silencing*
  • Heterochromatin
  • Histone Code / genetics
  • Homeodomain Proteins* / genetics
  • Homeodomain Proteins* / metabolism
  • Methylation
  • Neurospora crassa / genetics
  • Neurospora crassa / metabolism
  • Plant Proteins / genetics
  • Polycomb-Group Proteins* / genetics
  • Polycomb-Group Proteins* / metabolism

Substances

  • Fungal Proteins
  • Heterochromatin
  • Homeodomain Proteins
  • Plant Proteins
  • Polycomb-Group Proteins