title: Composite co-activator ARC mediates chromatin-directed transcriptional activation.
abstract: Gene activation in eukaryotes is regulated by complex mechanisms in which the recruitment and assembly of the transcriptional machinery is directed by gene- and cell-type-specific DNA-binding proteins. When DNA is packaged into chromatin, the regulation of gene activation requires new classes of chromatin-targeting activity. In humans, a multisubunit cofactor functions in a chromatin-selective manner to potentiate synergistic gene activation by the transcriptional activators SREBP-1a and Sp1. Here we show that this activator-recruited cofactor (ARC) interacts directly with several different activators, including SREBP-1a, VP16 and the p65 subunit of NF-kappaB, and strongly enhances transcription directed by these activators in vitro with chromatin-assembled DNA templates. The ARC complex consists of 16 or more subunits; some of these are novel gene products, whereas others are present in other multisubunit cofactors, such as CRSP, NAT and mammalian Mediator. Detailed analysis indicates that the ARC complex is probably identical to the nuclear hormone-receptor cofactor DRIP. Thus, ARC/DRIP is a large composite co-activator that belongs to a family of related cofactors and is targeted by different classes of activator to mediate transcriptional stimulation.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Näär
authors.forename: P A
authors.initials: PA
authors.lastname: Beaurang
authors.forename: S
authors.initials: S
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Abraham
authors.forename: W
authors.initials: W
authors.lastname: Solomon
authors.forename: R
authors.initials: R
authors.lastname: Tjian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D056892:Mediator Complex; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C117286:CRSP protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D046911:Macromolecular Substances; C538713:Med17 protein, human; D056892:Mediator Complex; D009687:Nuclear Proteins; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; C497387:SREBF1 protein, human; D016329:Sp1 Transcription Factor; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors