Université Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences (IAB), Site Santé - Allée des Alpes, 38700, La Tronche, France.
International Agency for Research on Cancer (IARC), 69008, Lyon, France.
Sci Rep. 2017 Jul 14;7(1):5418. doi: 10.1038/s41598-017-05343-8.
The heat shock response is characterized by the transcriptional activation of both hsp genes and noncoding and repeated satellite III DNA sequences located at pericentric heterochromatin. Both events are under the control of Heat Shock Factor I (HSF1). Here we show that under heat shock, HSF1 recruits major cellular acetyltransferases, GCN5, TIP60 and p300 to pericentric heterochromatin leading to a targeted hyperacetylation of pericentric chromatin. Redistribution of histone acetylation toward pericentric region in turn directs the recruitment of Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, BRD4, which are required for satellite III transcription by RNAP II. Altogether we uncover here a critical role for HSF1 in stressed cells relying on the restricted use of histone acetylation signaling over pericentric heterochromatin (HC).
热休克反应的特征是 hsp 基因和位于着丝粒异染色质的非编码和重复卫星 III DNA 序列的转录激活。这两个事件都受热休克因子 I(HSF1)的控制。在这里,我们表明在热休克下,HSF1 将主要的细胞乙酰转移酶 GCN5、TIP60 和 p300 招募到着丝粒异染色质,导致着丝粒染色质的靶向超乙酰化。组蛋白乙酰化向着丝粒区域的重新分布反过来又指导 Bromodomain and Extra-Terminal(BET)蛋白 BRD2、BRD3、BRD4 的募集,这些蛋白是 RNAP II 转录卫星 III 所必需的。总的来说,我们在这里揭示了 HSF1 在依赖于着丝粒异染色质(HC)上受限的组蛋白乙酰化信号的应激细胞中的关键作用。