Human ATAC Is a GCN5/PCAF-containing acetylase complex with a novel NC2-like histone fold module that interacts with the TATA-binding protein.
Eukaryotic GCN5 acetyltransferases influence diverse biological processes by acetylating histones and non-histone proteins and regulating chromatin and gene-specific transcription as part of multiprotein complexes. In lower eukaryotes and invertebrates, these complexes include the yeast ADA complex that is still incompletely understood; the SAGA (Spt-Ada-Gcn5 acetylase) complexes from yeast to Drosophila that are mostly coactivators; and the ATAC (Ada Two-A containing) complex, only known in Drosophila and still poorly characterized. In contrast, vertebrate organisms, express two paralogous GCN5-like acetyltransferases (GCN5 and PCAF), which have been found so far only in SAGA-type complexes referred to hereafter as the STAGA (SPT3-TAF9-GCN5/PCAF acetylase) complexes. We now report the purification and characterization of vertebrate (human) ATAC-type complexes and identify novel components of STAGA. We show that human ATAC complexes incorporate in addition to GCN5 or PCAF (GCN5/PCAF), other epigenetic coregulators (ADA2-A, ADA3, STAF36, and WDR5), cofactors of chromatin assembly/remodeling and DNA replication machineries (POLE3/CHRAC17 and POLE4), the stress- and TGFbeta-activated protein kinase (TAK1/MAP3K7) and MAP3-kinase regulator (MBIP), additional cofactors of unknown function, and a novel YEATS2-NC2beta histone fold module that interacts with the TATA-binding protein (TBP) and negatively regulates transcription when recruited to a promoter. We further identify the p38 kinase-interacting protein (p38IP/FAM48A) as a novel component of STAGA with distant similarity to yeast Spt20. These results suggest that vertebrate ATAC-type and STAGA-type complexes link specific extracellular signals to modification of chromatin structure and regulation of the basal transcription machinery.
Wang
Yuan-Liang
YL
Department of Biochemistry, University of California at Riverside, CA 92521, USA.
Faiola
Francesco
F
Xu
Muyu
M
Pan
Songqin
S
Martinez
Ernest
E
D000115:Acetylesterase / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D004330:Drosophila; D017930:Genes, Reporter; D051548:Histone Acetyltransferases / Q000737:chemistry*; D006657:Histones / Q000737:chemistry*; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D035181:TATA-Box Binding Protein / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D050880:p300-CBP Transcription Factors / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D000115:Acetylesterase; D051548:Histone Acetyltransferases; D006657:Histones; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D000099224:p300-CBP-Associated Factor; C075995:down-regulator of transcription 1; C501392:GCN5 protein, S cerevisiae