Chromodomain protein CDYL is required for transmission/restoration of repressive histone marks

J Mol Cell Biol. 2017 Jun 1;9(3):178-194. doi: 10.1093/jmcb/mjx013.

Abstract

Faithful transmission or restoration of epigenetic information such as repressive histone modifications through generations is critical for the maintenance of cell identity. We report here that chromodomain Y-like protein (CDYL), a chromodomain-containing transcription corepressor, is physically associated with chromatin assembly factor 1 (CAF-1) and the replicative helicase MCM complex. We showed that CDYL bridges CAF-1 and MCM, facilitating histone transfer and deposition during DNA replication. We demonstrated that CDYL recruits histone-modifying enzymes G9a, SETDB1, and EZH2 to replication forks, leading to the addition of H3K9me2/3 and H3K27me2/3 on newly deposited histone H3. Significantly, depletion of CDYL impedes early S phase progression and sensitizes cells to DNA damage. Our data indicate that CDYL plays an important role in the transmission/restoration of repressive histone marks, thereby preserving the epigenetic landscape for the maintenance of cell identity.

Keywords: CAF-1; CDYL; MCM; epigenetic inheritance; histone modification.

MeSH terms

  • Chromatin / metabolism
  • Co-Repressor Proteins
  • DNA Damage
  • DNA Replication*
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Epigenesis, Genetic
  • Histone-Lysine N-Methyltransferase
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Hydro-Lyases
  • Lysine / metabolism
  • Minichromosome Maintenance Proteins / metabolism
  • Protein Methyltransferases / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • S Phase / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • CNOT8 protein, human
  • Chromatin
  • Co-Repressor Proteins
  • Histones
  • Proteins
  • Transcription Factors
  • Protein Methyltransferases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Histone-Lysine N-Methyltransferase
  • SETDB1 protein, human
  • Minichromosome Maintenance Proteins
  • CDYL protein, human
  • Hydro-Lyases
  • Lysine