Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo

GCN5 is a histone acetyltransferase (HAT) originally identified in Saccharo myces cerevisiae and required for transcription of specific genes within ch romatin as part of the SAGA (SPT-ADA-GCN5 acetylase) coactivator complex. M ammalian cells have two distinct GCN5 homologs (PCAF and GCN5L) that have b een found in three different SAGA-like complexes (PCAF complex, TFTC [TATA- binding-protein-free TAF(Pi)-containing complex], and STAGA [SPT3-TAF(Pi)-G CN5L acetylase]). The composition and roles of these mammalian RAT complexe s are still poorly characterized. Here, we present the purification and cha racterization of the human STAGA complex. We show that STAGA contains homol ogs of most yeast SAGA components, including two novel human proteins with histone-like folds and sequence relationships to yeast SPT7 and ADA1. Furth ermore, we demonstrate that STAGA has acetyl coenzyme A-dependent transcrip tional coactivator functions from a chromatin-assembled template in vitro a nd associates in HeLa cells with spliceosome-associated protein 130 (SAP130 ) and DDB1, two structurally related proteins. SAP130 is a component of the splicing factor SF3b that associates with U2 snRNP and is recruited to pre spliceosomal complexes. DDB1 (p127) is a UV-damaged-DNA-binding protein tha t is involved, as part of a complex with DDB2 (p48), in nucleotide excision repair and the hereditary disease xeroderma pigmentosum. Our results thus suggest cellular roles of STAGA in chromatin modification, transcription, a nd transcription-coupled processes through direct physical interactions wit h sequence-specific transcription activators and with components of the spl icing and DNA repair machineries.