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) ? (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 GR? (a splice variant of GR?) and estrogen receptor ? (ER?), facilitating hormonal regulation of some genes and blocking hormonal regulation of others. As with GR?, Hic-5 blocking of hormonal gene regulation mediated by GR? and ER? was associated with blocking of GR? and ER? occupancy at nearby sites. Hic-5 supported hormonal regulation of many more genes for GR? than for GR? or ER? 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.

SUBMITTER: Chodankar R 

PROVIDER: S-EPMC4415210 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature