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

Yue Zhao; Guillaume Lang; Saya Ito; Jacques Bonnet; Eric Metzger; Shun Sawatsubashi; Eriko Suzuki; Xavier Le Guezennec; Hendrik G Stunnenberg; Aleksey Krasnov; Sofia G Georgieva; Roland Schüle; Ken-Ichi Takeyama; Shigeaki Kato; László Tora; Didier Devys

doi:10.1016/j.molcel.2007.12.011

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.

Authors

Yue Zhao¹, Guillaume Lang, Saya Ito, Jacques Bonnet, Eric Metzger, Shun Sawatsubashi, Eriko Suzuki, Xavier Le Guezennec, Hendrik G Stunnenberg, Aleksey Krasnov, Sofia G Georgieva, Roland Schüle, Ken-Ichi Takeyama, Shigeaki Kato, László Tora, Didier Devys

Affiliation

¹ Laboratory of Nuclear Signaling, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.

PMID: 18206972
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*
Ubiquitin Thiolesterase
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
Ubiquitin Thiolesterase
Usp22 protein, human