title: Core promoter-selective function of HMGA1 and Mediator in Initiator-dependent transcription.
abstract: The factors and mechanisms underlying the differential activity and regulation of eukaryotic RNA polymerase II on different types of core promoters have remained elusive. Here we show that the architectural factor HMGA1 and the Mediator coregulator complex cooperate to enhance basal transcription from core promoters containing both a TATA box and an Initiator (INR) element but not from "TATA-only" core promoters. INR-dependent activation by HMGA1 and Mediator requires the TATA-binding protein (TBP)-associated factors (TAFs) within the TFIID complex and counteracts negative regulators of TBP/TATA-dependent transcription such as NC2 and Topoisomerase I. HMGA1 interacts with TFIID and Mediator and is required for the synergy of TATA and INR elements in mammalian cells. Accordingly, natural HMGA1-activated genes in embryonic stem cells tend to have both TATA and INR elements in a synergistic configuration. Our results suggest a core promoter-specific regulation of Mediator and the basal transcription machinery by HMGA1.
authors.affiliation: Department of Biochemistry, University of California at Riverside, Riverside, California 92521, USA.
authors.forename: Muyu
authors.initials: M
authors.lastname: Xu
authors.forename: Priyanka
authors.initials: P
authors.lastname: Sharma
authors.forename: Songqin
authors.initials: S
authors.lastname: Pan
authors.forename: Sohail
authors.initials: S
authors.lastname: Malik
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
authors.forename: Ernest
authors.initials: E
authors.lastname: Martinez
mesh_terms: D057809:HEK293 Cells; D024003:HMGA Proteins / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D056892:Mediator Complex / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016385:TATA Box; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D024003:HMGA Proteins; D056892:Mediator Complex; D035181:TATA-Box Binding Protein; D035362:Transcription Factor TFIID