A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing

Mol Cell. 2008 Jan 18;29(1):92-101. doi: 10.1016/j.molcel.2007.12.011.

Abstract

Transcriptional activators, several different coactivators, and general transcription factors are necessary to access specific loci in the dense chromatin structure to allow precise initiation of RNA polymerase II (Pol II) transcription. Histone acetyltransferase (HAT) complexes were implicated in loosening the chromatin around promoters and thus in gene activation. Here we demonstrate that the 2 MDa GCN5 HAT-containing metazoan TFTC/STAGA complexes contain a histone H2A and H2B deubiquitinase activity. We have identified three additional subunits of TFTC/STAGA (ATXN7L3, USP22, and ENY2) that form the deubiquitination module. Importantly, we found that this module is an enhancer of position effect variegation in Drosophila. Furthermore, we demonstrate that ATXN7L3, USP22, and ENY2 are required as cofactors for the full transcriptional activity by nuclear receptors. Thus, the deubiquitinase activity of the TFTC/STAGA HAT complex is necessary to counteract heterochromatin silencing and acts as a positive cofactor for activation by nuclear receptors in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Conserved Sequence
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Endopeptidases / chemistry
  • Endopeptidases / genetics
  • Endopeptidases / physiology
  • Gene Silencing*
  • Heterochromatin / genetics*
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / physiology*
  • Humans
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / physiology
  • Promoter Regions, Genetic / genetics
  • Protein Interaction Mapping*
  • RNA Polymerase II / physiology
  • Receptors, Androgen / genetics*
  • Recombinant Fusion Proteins / physiology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Thiolester Hydrolases / chemistry
  • Thiolester Hydrolases / physiology
  • Trans-Activators / chemistry
  • Trans-Activators / physiology*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Transcription Factors, General / chemistry
  • Transcription Factors, General / physiology*
  • Transcription, Genetic / genetics*
  • Ubiquitination / physiology*
  • p300-CBP Transcription Factors / chemistry
  • p300-CBP Transcription Factors / physiology

Substances

  • ATXN7L3 protein, human
  • Drosophila Proteins
  • Eny2 protein, human
  • Heterochromatin
  • Multiprotein Complexes
  • Receptors, Androgen
  • Recombinant Fusion Proteins
  • Sgf11 protein, Drosophila
  • Trans-Activators
  • Transcription Factors
  • Transcription Factors, General
  • e(y)2 protein, Drosophila
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • RNA Polymerase II
  • Thiolester Hydrolases
  • Endopeptidases
  • not protein, Drosophila
  • Usp22 protein, human