Transcriptional response to stress is pre-wired by promoter and enhancer architecture.
Transcriptional response to stress is pre-wired by promoter and enhancer architecture.
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DOI：
10.1038/s41467-017-00151-0
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发表时间：
2017-08-15
影响因子：
16.6
通讯作者：
Sistonen L
中科院分区：
文献类型：
--
作者：
Vihervaara A;Mahat DB;Guertin MJ;Chu T;Danko CG;Lis JT;Sistonen L
基因表达程序由一组转录因子执行，这些转录因子协调来自一对紧密相连的启动子和增强子核心起始区的不同转录。在这里，为了研究不同转录如何在压力下重新编程，我们以核苷酸分辨率测量了新生 RNA 合成，并分析了人类细胞中的组蛋白 H4 乙酰化。我们在全球范围内的研究结果表明，启动子近端暂停的RNA聚合酶释放进入延伸是决定基因对应激反应的关键开关。高度转录和高度诱导的基因表现出强转录方向性和核心正义启动子上通用转录因子的选择性组装。相反，增强子处的热诱导转录与细胞类型、序列特异性转录因子的先前结合相关。激活的热休克因子 1 (HSF1) 与转录引发的启动子和增强子以及 CTCF 占据的非转录染色质结合。这些结果揭示了染色质结构特征，这些特征在不同的调控元件上定向转录并在全基因组范围内启动转录反应。热休克因子 1 (HSF1) 是应激诱导转录的调节因子。在这里，作者研究了应激时转录和染色质组织的变化，发现激活的 HSF1 与转录引发的启动子和增强子以及 CTCF 占据的非转录染色质结合。
Programs of gene expression are executed by a battery of transcription factors that coordinate divergent transcription from a pair of tightly linked core initiation regions of promoters and enhancers. Here, to investigate how divergent transcription is reprogrammed upon stress, we measured nascent RNA synthesis at nucleotide-resolution, and profiled histone H4 acetylation in human cells. Our results globally show that the release of promoter-proximal paused RNA polymerase into elongation functions as a critical switch at which a gene’s response to stress is determined. Highly transcribed and highly inducible genes display strong transcriptional directionality and selective assembly of general transcription factors on the core sense promoter. Heat-induced transcription at enhancers, instead, correlates with prior binding of cell-type, sequence-specific transcription factors. Activated Heat Shock Factor 1 (HSF1) binds to transcription-primed promoters and enhancers, and CTCF-occupied, non-transcribed chromatin. These results reveal chromatin architectural features that orient transcription at divergent regulatory elements and prime transcriptional responses genome-wide. Heat Shock Factor 1 (HSF1) is a regulator of stress-induced transcription. Here, the authors investigate changes to transcription and chromatin organization upon stress and find that activated HSF1 binds to transcription-primed promoters and enhancers, and to CTCF occupied, untranscribed chromatin.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
16
作者：
Fujiwara T;O'Geen H;Keles S;Blahnik K;Linnemann AK;Kang YA;Choi K;Farnham PJ;Bresnick EH
通讯作者：
Bresnick EH
影响因子：
46.9
作者：
He, Qiye;Johnston, Jeff;Zeitlinger, Julia
通讯作者：
Zeitlinger, Julia
DOI：
10.1074/jbc.m110.157552
发表时间：
2010-11-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Akerfelt M;Vihervaara A;Laiho A;Conter A;Christians ES;Sistonen L;Henriksson E
通讯作者：
Henriksson E