THE TRANSCRIPTIONALLY-ACTIVE MMTV PROMOTER IS DEPLETED OF HISTONE H1

THE TRANSCRIPTIONALLY-ACTIVE MMTV PROMOTER IS DEPLETED OF HISTONE H1
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DOI:
10.1093/nar/20.2.273
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发表时间:
1992-01-25
影响因子:
14.9
通讯作者:
HAGER, GL
HAGER, GL
中科院分区:
生物学2区
文献类型:
--
作者:
BRESNICK, EH;BUSTIN, M;HAGER, GL

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我们已经使用紫外光交联和免疫吸附实验来证明组蛋白H1和H2B与被抑制的MMTV启动子结合。激素激活导致H1含量降低,而H_2B含量变化很小或没有变化。对糖皮质激素诱导的DNasel超敏区的高分辨率分析表明,在核小体B和核小体B/核小体A连接子上存在NF-1足迹以及特定的增强切割位点。这些结果与糖皮质激素受体与核小体B表面糖皮质激素调节元件结合诱导染色质转变的模型一致,而染色质转变是转录因子(NF-1和TFIID)募集到MMTV启动子所必需的。我们假设,组蛋白H1与启动子上的重要顺式元件结合掩盖了这些位点,糖皮质激素诱导的H1置换是暴露核小体B的3‘边缘、核小体B/核小体A连接子和核小体A的5’边缘的因子结合位点所必需的。
We have used an ultraviolet light cross-linking and immunoadsorption assay to demonstrate that histones H1 and H2B are bound to the repressed MMTV promoter. Hormone activation results in reduced H1 content with little or no change in H2B. High resolution analysis of the glucocorticoid-inducible DNasel hypersensitive region demonstrates an NF-1 footprint as well as specific sites of enhanced cleavage on nucleosome B and in the nucleosome B/nucleosome A linker. These results are consistent with a model in which binding of the glucocorticoid receptor to glucocorticoid regulatory elements on the surface of nucleosome B induces a chromatin transition that is necessary for transcription factor (NF-1 and TFIID) recruitment to the MMTV promoter. We hypothesize that association of histone H1 with important cis-elements on the promoter masks these sites, and glucocorticoid-induced displacement of H1 is necessary to expose factor binding sites at the 3' edge of nucleosome B, in the nucleosome B/nucleosome A linker and at the 5' edge of nucleosome A.