Interaction of the glucocorticoid receptor with the chromatin landscape
Interaction of the glucocorticoid receptor with the chromatin landscape
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DOI：
10.1016/j.molcel.2008.02.010
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发表时间：
2008-03-14
期刊：
影响因子：
16
通讯作者：
Hager, Gordon L.
中科院分区：
文献类型：
--
作者：
John, Sam;Sabo, Peter J.;Hager, Gordon L.
核受体功能对染色质重塑的普遍性和范围尚不清楚。我们对糖皮质激素受体（GR）在GR诱导或抑制的基因上的结合事件以及染色质结构转变进行了表征。这项分析表明，GR结合总是发生在核酸酶可接近的位点（DHS）。然而，机制的显著多样性使得这些位点可供GR结合。GR结合位点的可接近性要么是组成性的，要么是激素诱导的。在每一类中，一些DHS位点需要含Brg1的Swi/Snf复合物，但其他位点不依赖于Brg1，这意味着存在不同的重塑复合物。H2A.Z组蛋白变体在诱导型和组成型DHS位点都高度富集，并且在激素激活过程中会发生交换。DHS图谱具有高度的细胞特异性，这表明染色质景观的细胞选择性组织是组织选择性受体功能的关键决定因素。此外，对染色质重塑的广泛需求支持了最近的一种假说，即受体蛋白的快速交换发生在核小体重组过程中。
The generality and spectrum of chromatin-remodeling requirements for nuclear receptor function are unknown. We have characterized glucocorticoid receptor(GR) binding events and chromatin structural transitions across GR-induced or -repressed genes. This analysis reveals that GR binding invariably occurs at nuclease-accessible sites (DHS). A remarkable diversity of mechanisms, however, render these sites available for GR binding. Accessibility of the GR binding sites is either constitutive or hormone inducible. Within each category, some DHS sites require the Brg1-containing Swi/Snf complex, but others are Brg1 independent, implicating a different remodeling complex. The H2A.Z histone variant is highly enriched at both inducible and constitutive DHS sites and is subject to exchange during hormone activation. The DHS profile is highly cell specific, implicating cell-selective organization of the chromatin landscape as a critical determinant of tissue-selective receptor function. Furthermore, the widespread requirement for chromatin remodeling supports the recent hypothesis that the rapid exchange of receptor proteins occurs during nucleosome reorganization.