ISWI chromatin remodeling complexes recruit NSD2 and H3K36me2 in pericentromeric heterochromatin

J Cell Biol. 2024 Aug 5;223(8):e202310084. doi: 10.1083/jcb.202310084. Epub 2024 May 6.

Abstract

Histone H3 lysine36 dimethylation (H3K36me2) is generally distributed in the gene body and euchromatic intergenic regions. However, we found that H3K36me2 is enriched in pericentromeric heterochromatin in some mouse cell lines. We here revealed the mechanism of heterochromatin targeting of H3K36me2. Among several H3K36 methyltransferases, NSD2 was responsible for inducing heterochromatic H3K36me2. Depletion and overexpression analyses of NSD2-associating proteins revealed that NSD2 recruitment to heterochromatin was mediated through the imitation switch (ISWI) chromatin remodeling complexes, such as BAZ1B-SMARCA5 (WICH), which directly binds to AT-rich DNA via a BAZ1B domain-containing AT-hook-like motifs. The abundance and stoichiometry of NSD2, SMARCA5, and BAZ1B could determine the localization of H3K36me2 in different cell types. In mouse embryos, H3K36me2 heterochromatin localization was observed at the two- to four-cell stages, suggesting its physiological relevance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases
  • Animals
  • Bromodomain Containing Proteins / genetics
  • Bromodomain Containing Proteins / metabolism
  • Centromere / genetics
  • Centromere / metabolism
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Heterochromatin* / genetics
  • Heterochromatin* / metabolism
  • Histone-Lysine N-Methyltransferase* / genetics
  • Histone-Lysine N-Methyltransferase* / metabolism
  • Histones* / genetics
  • Histones* / metabolism
  • Humans
  • Methylation
  • Mice
  • Repressor Proteins* / genetics
  • Repressor Proteins* / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Adenosine Triphosphatases
  • BAZ1B protein, human
  • Bromodomain Containing Proteins
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Histone-Lysine N-Methyltransferase
  • Histones
  • NSD2 protein, human
  • Repressor Proteins
  • SMARCA5 protein, human
  • Smarca5 protein, mouse
  • Transcription Factors
  • WHSC1 protein, mouse
  • Baz1b protein, mouse