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

被引：303

作者：

Zhao, Yue ^{[2
]}

Lang, Guillaume ^{[1
]}

Ito, Saya ^{[2
]}

Bonnet, Jacques ^{[1
]}

Metzger, Eric ^{[3
,4
]}

Sawatsubashi, Shun ^{[2
]}

Suzuki, Eriko ^{[2
]}

Le Guezennec, Xavier ^{[5
]}

Stunnenberg, Hendrilk G. ^{[5
]}

Krasnov, Aleksey ^{[6
]}

Georgieva, Sofia G. ^{[6
]}

Schuele, Roland ^{[3
,4
]}

Takeyama, Ken-Ichi ^{[2
]}

Kato, Shigeaki ^{[2
]}

Tora, Laszlo ^{[1
]}

Devys, Didier ^{[1
]}

机构：

[1] Univ Strasbourg 1, INSERM, U596,UMR 7104, CNRS,Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

[2] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Nucl Signalling, Bunkyo Ku, Tokyo 1130032, Japan

[3] Univ Freiburg Klinikum, Zentrum Klin Forsch, D-79106 Freiburg, Germany

[4] Univ Frauenklin, D-79106 Freiburg, Germany

[5] Radboud Univ Nijmigen, NCMLS, Dept Mol Biol, NL-6500 HB Nijmegen, Netherlands

[6] Russian Acad Sci, Inst Gene Biol, Moscow 119334, Russia

来源：

MOLECULAR CELL | 2008年 / 29卷 / 01期

关键词：

D O I：

10.1016/j.molcel.2007.12.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 11 (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.

引用

页码：92 / 101

页数：10

共 31 条

[1] SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope [J].