Glucocorticoid receptor-promoter interactions: energetic dissection suggests a framework for the specificity of steroid receptor-mediated gene regulation.

Biochemistry
James P RobbleeDavid L Bain

Abstract

The glucocorticoid receptor (GR) is a member of the steroid receptor family of ligand-activated transcription factors. A number of studies have shown that steroid receptors regulate distinct but overlapping sets of genes; however, the molecular basis for such specificity remains unclear. Previous work from our laboratory has demonstrated that under identical solution conditions, three other steroid receptors [the progesterone receptor A isoform (PR-A), the progesterone receptor B isoform (PR-B), and estrogen receptor α (ER-α)] differentially partition their self-association and promoter binding energetics. For example, PR-A and PR-B generate similar dimerization free energies but differ significantly in their extents of intersite cooperativity. Conversely, ER-α maintains an intersite cooperativity most comparable to that of PR-A yet dimerizes with an affinity orders of magnitude greater than that of either of the PR isoforms. We have speculated that these differences serve to generate receptor-specific promoter occupancies, and thus receptor-specific gene regulation. Noting that GR regulates a unique subset of genes relative to the other receptors, we hypothesized that the receptor should maintain a unique set of interaction en...Continue Reading

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Citations

Dec 12, 2012·Nature Structural & Molecular Biology·William H HudsonEric A Ortlund
Jun 4, 2013·Nature Structural & Molecular Biology·Lisa C WatsonKeith R Yamamoto
Dec 17, 2015·Annual Review of Physiology·Maria A SactaInez Rogatsky
Jan 6, 2017·Nature Reviews. Molecular Cell Biology·Emily R WeikumKeith R Yamamoto
Apr 8, 2018·Nature Communications·William H HudsonEric A Ortlund
Dec 11, 2020·Nature·Georg K A HochbergJoseph W Thornton

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