TY - JOUR
T1 - A TFTC/STAGA Module Mediates Histone H2A and H2B Deubiquitination, Coactivates Nuclear Receptors, and Counteracts Heterochromatin Silencing
AU - Zhao, Yue
AU - Lang, Guillaume
AU - Ito, Saya
AU - Bonnet, Jacques
AU - Metzger, Eric
AU - Sawatsubashi, Shun
AU - Suzuki, Eriko
AU - Le Guezennec, Xavier
AU - Stunnenberg, Hendrik G.
AU - Krasnov, Aleksey
AU - Georgieva, Sofia G.
AU - Schüle, Roland
AU - Takeyama, Ken Ichi
AU - Kato, Shigeaki
AU - Tora, László
AU - Devys, Didier
N1 - Funding Information:
We thank D. Helmlinger, O. Bombarde, M. Vermeulen, M. Oulad-Abdelghani, and G. Duval for their contribution to this work. We thank Z. Nagy and M.E. Torres Padilla for critically reading the manuscript, and R.G. Roeder, I. Dikic, T. Nagase, and E. Martinez for generous gifts of different reagents. Research in the authors' laboratory is supported by grants from the the Agence Nationale de la Recherche (ANR-05-MRAR-O29-01), from the Fondation de la Recherche Médicale (FRM, DLC20060206408), and from Connaitre les Syndromes Cerebelleux to D.D. and from ANR (05-BLAN-0396-01; Regulome), European Community (HPRN-CT 00504228 and STREP LSHG-CT-2004-502950) to L.T.
PY - 2008/1/18
Y1 - 2008/1/18
N2 - 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.
AB - 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.
KW - DNA
UR - https://www.scopus.com/pages/publications/38149068875
U2 - 10.1016/j.molcel.2007.12.011
DO - 10.1016/j.molcel.2007.12.011
M3 - Article
C2 - 18206972
AN - SCOPUS:38149068875
SN - 1097-2765
VL - 29
SP - 92
EP - 101
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -