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Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5745-9. doi: 10.1073/pnas.0801551105. Epub 2008 Apr 11.

Conservation analysis predicts in vivo occupancy of glucocorticoid receptor-binding sequences at glucocorticoid-induced genes.

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1
Department of Cellular and Molecular Pharmacology, Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94518-2517, USA.

Abstract

The glucocorticoid receptor (GR) interacts with specific GR-binding sequences (GBSs) at glucocorticoid response elements (GREs) to orchestrate transcriptional networks. Although the sequences of the GBSs are highly variable among different GREs, the precise sequence within an individual GRE is highly conserved. In this study, we examined whether sequence conservation of sites resembling GBSs is sufficient to predict GR occupancy of GREs at genes responsive to glucocorticoids. Indeed, we found that the level of conservation of these sites at genes up-regulated by glucocorticoids in mouse C3H10T1/2 mesenchymal stem-like cells correlated directly with the extent of occupancy by GR. In striking contrast, we failed to observe GR occupancy of GBSs at genes repressed by glucocorticoids, despite the occurrence of these sites at a frequency similar to that of the induced genes. Thus, GR occupancy of the GBS motif correlates with induction but not repression, and GBS conservation alone is sufficient to predict GR occupancy and GRE function at induced genes.

PMID:
18408151
PMCID:
PMC2311370
DOI:
10.1073/pnas.0801551105
[Indexed for MEDLINE]
Free PMC Article
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