A Modular Ligation Strategy for Asymmetric Bivalent Nucleosomes Trimethylated at K36 and K27

Chembiochem. 2019 May 2;20(9):1124-1128. doi: 10.1002/cbic.201800744. Epub 2019 Mar 12.

Abstract

In nature, individual histones in the same nucleosome can carry identical (symmetric) or different (asymmetric) post-translational modification (PTM) patterns, increasing the combinatorial complexity. Embryonic stem cells exhibit "bivalent" nucleosomes, some of which are marked by an asymmetric arrangement of H3K36me3 (an activating PTM) and H3K27me3 (a repressive PTM). Here we describe a modular synthetic method to access such asymmetrically modified nucleosomes and show that H3K36me3 inhibits the activity of the methyltransferase PRC2 locally while still prolonging its chromatin binding time.

Keywords: asymmetric nucleosomes; bivalent domains; epigenetics; expressed protein ligation; protein modifications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disulfides / chemical synthesis
  • Disulfides / chemistry
  • Histones / chemical synthesis
  • Histones / chemistry*
  • Histones / metabolism
  • Humans
  • Lysine / chemistry
  • Methylation
  • Nucleosomes / chemistry*
  • Nucleosomes / metabolism
  • Polycomb Repressive Complex 2 / chemistry
  • Polycomb Repressive Complex 2 / metabolism
  • Protein Binding

Substances

  • Disulfides
  • Histones
  • Nucleosomes
  • Polycomb Repressive Complex 2
  • Lysine