H2A Ubiquitination Alters H3-tail Dynamics on Linker-DNA to Enhance H3K27 Methylation

J Mol Biol. 2023 Feb 28;435(4):167936. doi: 10.1016/j.jmb.2022.167936. Epub 2023 Jan 4.

Abstract

Polycomb repressive complex 1 (PRC1) and PRC2 are responsible for epigenetic gene regulation. PRC1 ubiquitinates histone H2A (H2Aub), which subsequently promotes PRC2 to introduce the H3 lysine 27 tri-methyl (H3K27me3) repressive chromatin mark. Although this mechanism provides a link between the two key transcriptional repressors, PRC1 and PRC2, it is unknown how histone-tail dynamics contribute to this process. Here, we have examined the effect of H2A ubiquitination and linker-DNA on H3-tail dynamics and H3K27 methylation by PRC2. In naïve nucleosomes, the H3-tail dynamically contacts linker DNA in addition to core DNA, and the linker-DNA is as important for H3K27 methylation as H2A ubiquitination. H2A ubiquitination alters contacts between the H3-tail and DNA to improve the methyltransferase activity of the PRC2-AEBP2-JARID2 complex. Collectively, our data support a model in which H2A ubiquitination by PRC1 synergizes with linker-DNA to hold H3 histone tails poised for their methylation by PRC2-AEBP2-JARID2.

Keywords: H2A ubiquitination; H3K27 methylation; NMR; histone tail; polycomb repressive complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry
  • Histones* / chemistry
  • Histones* / genetics
  • Methylation
  • Polycomb Repressive Complex 1* / chemistry
  • Polycomb Repressive Complex 1* / genetics
  • Polycomb Repressive Complex 2* / chemistry
  • Polycomb Repressive Complex 2* / genetics
  • Ubiquitination*

Substances

  • DNA
  • Histones
  • Polycomb Repressive Complex 1
  • Polycomb Repressive Complex 2
  • JARID2 protein, human
  • AEBP2 protein, human