RPA Assists HSF1 Access to Nucleosomal DNA by Recruiting Histone Chaperone FACT
RPA Assists HSF1 Access to Nucleosomal DNA by Recruiting Histone Chaperone FACT
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DOI：
10.1016/j.molcel.2012.07.026
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发表时间：
2012-10-26
期刊：
影响因子：
16
通讯作者：
Nakai, Akira
中科院分区：
文献类型：
--
作者：
Fujimoto, Mitsuaki;Takaki, Eiichi;Nakai, Akira
核小体阻止转录因子接近调节元件。热休克因子1（HSF 1）是一种有翼螺旋转录因子，在调控和应激条件下通过接近靶元件发挥作用，但在哺乳动物细胞中HSF 1的接近机制尚不清楚。在这里，我们展示了人类HSF 1的翼基序和复制蛋白A（RPA），这是参与DNA代谢之间的物理相互作用。RPA 1的缺失在非应激条件下废除了HSF 1对HSP 70启动子的访问，并延迟了其响应热休克的快速激活。HSF 1-RPA复合物导致RNA聚合酶II的预加载，并通过招募组蛋白伴侣FACT打开染色质结构。此外，这种相互作用是黑素瘤细胞增殖所必需的。这些结果提供了组成型HSF 1进入核小体DNA的机制，这对基础和诱导基因表达都很重要。
Transcription factor access to regulatory elements is prevented by the nucleosome. Heat shock factor 1 (HSF1) is a winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements, but mechanisms of HSF1 access are not well known in mammalian cells. Here, we show the physical interaction between the wing motif of human HSF1 and replication protein A (RPA), which is involved in DNA metabolism. Depletion of RPA1 abolishes HSF1 access to the promoter of HSP70 in unstressed condition and delays its rapid activation in response to heat shock. The HSF1-RPA complex leads to preloading of RNA polymerase II and opens the chromatin structure by recruiting a histone chaperone, FACT. Furthermore, this interaction is required for melanoma cell proliferation. These results provide a mechanism of constitutive HSF1 access to nucleosomal DNA, Which is important for both basal and inducible gene expression.