Glucocorticoid receptor activation of the IκBα promoter within chromatin
Glucocorticoid receptor activation of the IκBα promoter within chromatin
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DOI：
10.1091/mbc.12.11.3365
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发表时间：
2001-11-01
影响因子：
3.3
通讯作者：
Archer, TK
中科院分区：
文献类型：
--
作者：
Deroo, BJ;Archer, TK
The glucocorticoid receptor (GR) is a ligand-activated transcription factor that induces expression of many genes. The GR has been useful for understanding how chromatin structure regulates steroid-induced transcription in model systems. However, the effect of glucocorticoids on chromatin structure has been examined on few endogenous mammalian promoters. We investigated the effect of glucocorticoids on the in vivo chromatin structure of the glucocorticoid-responsive I kappaB alpha gene promoter, the inhibitor of the ubiquitous transcription factor, nuclear factor kappa B (NF kappaB). Glucocorticoids inhibit NF kappaB activity in some tissues by elevating the levels Of I kappaB alpha. We found that glucocorticoids activated the I kappaB alpha promoter in human T47D/A1-2 cells containing the GR. We then investigated the chromatin structure of the I kappaB alpha promoter in the absence and presence of glucocorticoids with the use of micrococcal nuclease, restriction enzyme, and deoxyribonuclease (DNasel) analyses. In untreated cells, the promoter assembles into regularly positioned nucleosomes, and glucocorticoid treatment did not alter nucleosomal position. Restriction enzyme accessiblity studies indicated that the I kappaB alpha promoter is assembled as phased nucleosomes that adopt an "open" chromatin architecture in the absence of hormone. However, glucocorticoids may be required for transcription factor binding, because DNaseI footprinting studies suggested that regulatory factors bind to the promoter upon glucocorticoid treatment.
