title: A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing.
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.
authors.affiliation: Laboratory of Nuclear Signaling, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lang
authors.forename: Saya
authors.initials: S
authors.lastname: Ito
authors.forename: Jacques
authors.initials: J
authors.lastname: Bonnet
authors.forename: Eric
authors.initials: E
authors.lastname: Metzger
authors.forename: Shun
authors.initials: S
authors.lastname: Sawatsubashi
authors.forename: Eriko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Xavier
authors.initials: X
authors.lastname: Le Guezennec
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Aleksey
authors.initials: A
authors.lastname: Krasnov
authors.forename: Sofia G
authors.initials: SG
authors.lastname: Georgieva
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
authors.forename: László
authors.initials: L
authors.lastname: Tora
authors.forename: Didier
authors.initials: D
authors.lastname: Devys
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D020868:Gene Silencing; D006570:Heterochromatin / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D025941:Protein Interaction Mapping; D012319:RNA Polymerase II / Q000502:physiology; D011944:Receptors, Androgen / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D035165:Transcription Factors, General / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics*; D043222:Ubiquitin Thiolesterase; D054875:Ubiquitination / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000737:chemistry / Q000502:physiology; D000099224:p300-CBP-Associated Factor
chemical_list: D029721:Drosophila Proteins; D010450:Endopeptidases; D006570:Heterochromatin; D051548:Histone Acetyltransferases; D046912:Multiprotein Complexes; D012319:RNA Polymerase II; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D013869:Thiolester Hydrolases; D015534:Trans-Activators; D014157:Transcription Factors; D035165:Transcription Factors, General; D043222:Ubiquitin Thiolesterase; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C527169:ATXN7L3 protein, human; C527171:Eny2 protein, human; C527172:Sgf11 protein, Drosophila; C423782:e(y)2 protein, Drosophila; C421164:not protein, Drosophila; C527170:Usp22 protein, human