Transcriptional regulation of HSF1 by RPA

热休克因子1（HSF 1）通过接近靶元件在控制和应激条件下发挥作用，但HSF 1接近哺乳动物细胞的机制尚不清楚。我发现了人类HSF 1的翼基序和复制蛋白A（RPA）之间的物理相互作用，这是参与DNA代谢。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。

Heat shock factor 1 (HSF1) 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. I found 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.