title: Selective coregulator function and restriction of steroid receptor chromatin occupancy by Hic-5.
abstract: Steroid receptors (SRs) bind specific DNA regulatory sequences, thereby activating and repressing gene expression. We previously showed that transcriptional coregulator Hic-5 facilitates glucocorticoid regulation of some genes but blocks glucocorticoid regulation of others. Here, in a genome-wide analysis, Hic-5 depletion dramatically increased the global number of sites occupied by glucocorticoid receptor (GR) α (the major GR isoform), and many binding sites blocked by Hic-5 were associated with genes for which Hic-5 also blocked glucocorticoid-regulated expression. Hic-5 had similar effects on GRγ (a splice variant of GRα) and estrogen receptor α (ERα), facilitating hormonal regulation of some genes and blocking hormonal regulation of others. As with GRα, Hic-5 blocking of hormonal gene regulation mediated by GRγ and ERα was associated with blocking of GRγ and ERα occupancy at nearby sites. Hic-5 supported hormonal regulation of many more genes for GRα than for GRγ or ERα and thus exhibited selective coregulator functions for different SRs. In contrast, the number of Hic-5-blocked genes was similar for all 3 SRs. In addition to classic coregulator activity, Hic-5 influences the genomic occupancy of multiple SRs and thereby blocks some aspects of hormonal regulation. Thus, Hic-5, because of its tissue-specific expression, could contribute to tissue-specific genomic occupancy and gene regulation by SRs.
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089-9176.
authors.forename: Rajas
authors.initials: R
authors.lastname: Chodankar
authors.forename: Dai-Ying
authors.initials: DY
authors.lastname: Wu
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Gerke
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stallcup
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D004958:Estradiol / Q000502:physiology; D015870:Gene Expression; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000502:physiology*
chemical_list: D002843:Chromatin; D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; C490351:TGFB1I1 protein, human; D004958:Estradiol