WAC, a functional partner of RNF20/40, regulates histone H2B ubiquitination and gene transcription

Mol Cell. 2011 Feb 18;41(4):384-97. doi: 10.1016/j.molcel.2011.01.024.

Abstract

Histone H2B ubiquitination plays an important role in regulating chromatin organization during gene transcription. It has been shown that RNF20/40 regulates H2B ubiquitination. Here, using protein affinity purification, we have identified WAC as a functional partner of RNF20/40. Depletion of WAC abolishes H2B ubiquitination. WAC interacts with RNF20/40 through its C-terminal coiled-coil region and promotes RNF20/40 s E3 ligase activity for H2B ubiquitination. The N-terminal WW domain of WAC recognizes RNA polymerase II. During gene transcription, WAC targets RNF20/40 to associate with RNA polymerase II complex for H2B ubiquitination at active transcription sites, which regulates transcription. Moreover, WAC-dependent transcription is important for cell-cycle checkpoint activation in response to genotoxic stress. Taken together, our results demonstrate an important regulator for transcription-coupled histone H2B ubiquitination.

Publication types

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

MeSH terms

  • Cells, Cultured
  • Gene Expression Regulation*
  • Genes, cdc
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Transcription Initiation Site
  • Transcription, Genetic*
  • Ubiquitin / genetics
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination

Substances

  • Histones
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • RNA Polymerase II