1. A TFTC/STAGA Module Mediates Histone H2A and H2B Deubiquitination, Coactivates Nuclear Receptors, and Counteracts Heterochromatin Silencing
- Author
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Didier Devys, Hendrik G. Stunnenberg, Ken-ichi Takeyama, Yue Zhao, Shigeaki Kato, Laszlo Tora, Xavier Le Guezennec, Roland Schüle, Shun Sawatsubashi, Eric Metzger, Jacques Bonnet, Sofia G. Georgieva, Eriko Suzuki, Guillaume Lang, Aleksey N. Krasnov, Saya Ito, Peney, Maité, Laboratory of Nuclear Signaling, The University of Tokyo (UTokyo)-Institute of Molecular and Cellular Biosciences, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universitäts-Frauenklinik und Zentrum für Klinische Forschung, Klinikum der Universität Freiburg, Department of Molecular Biology [Nijmegen], Radboud University Medical Center [Nijmegen], Institute of Gene Biology, Russian Academy of Sciences [Moscow] (RAS), and Institute of Molecular and Cellular Biosciences-The University of Tokyo (UTokyo)
- Subjects
Transcription, Genetic ,MESH: Sequence Homology, Amino Acid ,RNA polymerase II ,MESH: Amino Acid Sequence ,Animals, Genetically Modified ,MESH: Histone Acetyltransferases ,0302 clinical medicine ,Heterochromatin ,Protein Interaction Mapping ,Drosophila Proteins ,MESH: Animals ,MESH: Gene Silencing ,p300-CBP Transcription Factors ,MESH: Endopeptidases ,Promoter Regions, Genetic ,Conserved Sequence ,Histone Acetyltransferases ,0303 health sciences ,MESH: Conserved Sequence ,biology ,General transcription factor ,MESH: Transcription Factors ,Position-effect variegation ,MESH: p300-CBP Transcription Factors ,3. Good health ,Chromatin ,SAGA complex ,MESH: Promoter Regions (Genetics) ,MESH: Heterochromatin ,Drosophila melanogaster ,Receptors, Androgen ,030220 oncology & carcinogenesis ,MESH: Receptors, Androgen ,MESH: Thiolester Hydrolases ,RNA Polymerase II ,Transcription Factors, General ,Ubiquitin Thiolesterase ,MESH: Trans-Activators ,MESH: Drosophila Proteins ,Recombinant Fusion Proteins ,Molecular Sequence Data ,MESH: Sequence Alignment ,MESH: Transcription Factors, General ,MESH: Drosophila melanogaster ,Cell Line ,MESH: Animals, Genetically Modified ,03 medical and health sciences ,Histone H2A ,Endopeptidases ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,MESH: Recombinant Fusion Proteins ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Amino Acid Sequence ,Gene Silencing ,Molecular Biology ,030304 developmental biology ,MESH: Humans ,MESH: Molecular Sequence Data ,Sequence Homology, Amino Acid ,MESH: Transcription, Genetic ,MESH: Protein Interaction Mapping ,Ubiquitination ,Histone acetyltransferase ,Cell Biology ,MESH: Multiprotein Complexes ,Molecular biology ,MESH: RNA Polymerase II ,MESH: Cell Line ,Multiprotein Complexes ,biology.protein ,Trans-Activators ,MESH: Ubiquitination ,Thiolester Hydrolases ,Sequence Alignment ,Transcription Factors - Abstract
International audience; 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.
- Published
- 2008
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