Chromatin remodelers fine-tune H3K36me-directed deacetylation of neighbor nucleosomes by Rpd3S

Mol Cell. 2013 Oct 24;52(2):255-63. doi: 10.1016/j.molcel.2013.08.024. Epub 2013 Sep 19.

Abstract

Chromatin remodelers have been implicated in the regulation of histone-modifying complexes. However, the underlying mechanism remains poorly understood. The Rpd3S histone deacetylase complex is recruited by elongating RNA polymerase II to remove histone acetylation at coding regions in a manner that is dependent on methylation of lysine 36 on histone 3 (H3K36me), and Rpd3S prefers dinucleosomes. Here, we show that the binding of Rpd3S to dinucleosomes and its catalytic activity are sensitive to the length of nucleosomal linker in a nonlinear fashion. Intriguingly, we found that H3K36me on one nucleosome stimulates Rpd3S to deacetylate the neighboring nucleosomes when those two nucleosomes are within an optimal distance. Finally, we demonstrate that chromatin remodelers enhance Rpd3S activity by altering nucleosomal spacing, suggesting that chromatin remodelers prime chromatin configuration to fine-tune subsequent histone modification reactions. This mechanism is important for accurate temporal control of chromatin dynamics during the transcription elongation cycle.

Publication types

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

MeSH terms

  • Acetylation
  • Animals
  • Blotting, Western
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism*
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism
  • HeLa Cells
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Histones / metabolism*
  • Humans
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Models, Genetic
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Protein Binding
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription, Genetic

Substances

  • Chromatin
  • DNA, Fungal
  • Histones
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Methyltransferases
  • Set2 protein, S cerevisiae
  • RNA Polymerase II
  • RPD3 protein, S cerevisiae
  • Histone Deacetylases