Phosphorylation of histone H3(T118) alters nucleosome dynamics and remodeling

Nucleic Acids Res. 2011 Aug;39(15):6465-74. doi: 10.1093/nar/gkr304. Epub 2011 May 16.

Abstract

Nucleosomes, the fundamental units of chromatin structure, are regulators and barriers to transcription, replication and repair. Post-translational modifications (PTMs) of the histone proteins within nucleosomes regulate these DNA processes. Histone H3(T118) is a site of phosphorylation [H3(T118ph)] and is implicated in regulation of transcription and DNA repair. We prepared H3(T118ph) by expressed protein ligation and determined its influence on nucleosome dynamics. We find H3(T118ph) reduces DNA-histone binding by 2 kcal/mol, increases nucleosome mobility by 28-fold and increases DNA accessibility near the dyad region by 6-fold. Moreover, H3(T118ph) increases the rate of hMSH2-hMSH6 nucleosome disassembly and enables nucleosome disassembly by the SWI/SNF chromatin remodeler. These studies suggest that H3(T118ph) directly enhances and may reprogram chromatin remodeling reactions.

Publication types

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

MeSH terms

  • Chromatin Assembly and Disassembly*
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • MutS Homolog 2 Protein / metabolism
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism*
  • Phosphorylation
  • Protein Binding

Substances

  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • Histones
  • Nucleosomes
  • DNA
  • MSH2 protein, human
  • MutS Homolog 2 Protein