Glucocorticoid receptor-promoter interactions: energetic dissection suggests a framework for the specificity of steroid receptor-mediated gene regulation.
Glucocorticoid receptor-promoter interactions: energetic dissection suggests a framework for the specificity of steroid receptor-mediated gene regulation.
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DOI：
10.1021/bi3003956
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发表时间：
2012-06-05
期刊：
影响因子：
2.9
通讯作者：
Bain DL
中科院分区：
文献类型：
--
作者：
Robblee JP;Miura MT;Bain DL
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 inter-site cooperativity. Conversely, ER-α maintains inter-site cooperativity most comparable to PR-A, yet dimerizes with an affinity orders of magnitude greater than 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 energetics. We rigorously determined the self-association and promoter binding energetics of full-length, human GR under conditions identical to those used in our earlier studies. We find that unlike all other receptors, GR shows no evidence of reversible self-association. Moreover, GR assembles with strong inter-site cooperativity comparable to that seen only for PR-B. Finally, simulations show that such partitioning of interaction energetics allows for receptor-specific promoter occupancies, even under conditions where multiple receptors are competing for binding at identical sites.
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影响因子：
2.9
作者：
Moody, Amie D.;Miura, Michael T.;Bain, David L.
通讯作者：
Bain, David L.
影响因子：
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通讯作者：
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作者：
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通讯作者：
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通讯作者：
Churchill, Mair E. A.