Prolonged glucocorticoid exposure dephosphouylates histone H1 and inactivates the MMTV promoter
Prolonged glucocorticoid exposure dephosphouylates histone H1 and inactivates the MMTV promoter
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DOI：
10.1093/emboj/17.5.1454
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发表时间：
1998-03-02
期刊：
影响因子：
11.4
通讯作者：
Archer, TK
中科院分区：
文献类型：
--
作者：
Lee, HL;Archer, TK
糖皮质激素通过糖皮质激素受体（GR）介导的染色质破坏事件快速诱导小鼠乳腺肿瘤病毒（MMTV）启动子的转录。这种染色质的重塑是短暂的，使得在长时间暴露于激素时，启动子变得对糖皮质激素不敏感。我们证明，这种不敏感状态需要激素的持续存在，并且可以在其去除时逆转。我们的实验表明，启动子是通过一种机制，使组蛋白H1去磷酸化，响应糖皮质激素失活。糖皮质激素的去除导致组蛋白H1的再磷酸化和启动子的转录能力的重新获得。这种反应是特定的MMTV启动子组装成染色质，并没有观察到另一个诱导基因或瞬时转染的MMTV DNA。最后，我们证明，当MMTV启动子对糖皮质激素无反应时，MMTV启动子上的H1被去磷酸化。这些研究表明，磷酸化的H1与GR介导的MMTV染色质在体内的破坏密切相关。
Glucocorticoids rapidly induce transcription from the mouse mammary tumour virus (MMTV) promoter via a glucocorticoid receptor (GR)-mediated chromatin disruption event, This remodelling of chromatin is transient such that upon prolonged exposure to hormone the promoter becomes refractory to glucocorticoids, We demonstrate that this refractory state requires the continual presence of hormone and can be reversed lay its removal. Our experiments show that the promoter is inactivated via a mechanism whereby histone H1 is dephosphorylated in response to glucocorticoids. Removal of glucocorticoids results in the rephosphorylation of histone H1 and the reacquisition of transcriptional competence by the promoter. This response is specific for the MMTV promoter assembled as chromatin and is not observed for another inducible gene or transiently transfected MMTV DNA. Finally, we demonstrate that H1 on the MMTV promoter is dephosphorylated when the promoter is unresponsive to glucocorticoids, These studies indicate that phosphorylated H1 is intimately linked with the GR-mediated disruption of MMTV chromatin in vivo.