title: Sequential recruitment of steroid receptor coactivator-1 (SRC-1) and p300 enhances progesterone receptor-dependent initiation and reinitiation of transcription from chromatin.
abstract: Employing a cell-free chromatin transcription system that recapitulates progesterone receptor (PR)-mediated transcription in vivo, we have investigated further the coactivator functions of steroid receptor coactivator-1 (SRC-1) in terms of its functional domains as well as cooperation with other coactivators in PR transactivation. By analyzing wild-type and mutant SRC-1 with liganded PR in the chromatin transcription system in vitro, the basic helix-loop-helix/Per-Arnt-Sim domain, the p300-binding domain, and the carboxyl-terminal region (containing the PR-binding site) of SRC-1 were shown to be important for PR transactivation. Although in context of a synthetic promoter its histone acetyltransferase activity was nonessential for PR-mediated transcription, SRC-1 was observed to act synergistically with p300 to enhance PR transactivation from chromatin. Moreover, SRC-1 and p300 were found to function cooperatively to increase the efficiency of productive transcription initiation and reinitiation. Further analysis of synergism between SRC-1 and p300 revealed an obligatory "sequential" recruitment of SRC-1 and p300 to liganded PR. Efficient recruitment of p300 required the presence of SRC-1. In addition, functional analysis of SRC-2 and SRC-3 coactivators indicated that the SRC family modulated PR transactivation from chromatin by a similar mechanism.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: S Y
authors.initials: SY
authors.lastname: Tsai
authors.forename: M J
authors.initials: MJ
authors.lastname: Tsai
authors.forename: B W
authors.initials: BW
authors.lastname: O'Malley
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins; D011980:Receptors, Progesterone / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D015513:Oncogene Proteins; D011980:Receptors, Progesterone; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C025231:sarkosyl; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538866:NCOA3 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D012521:Sarcosine