Disruption of downstream chromatin directed by a transcriptional activator
Disruption of downstream chromatin directed by a transcriptional activator
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DOI：
10.1101/gad.11.23.3116
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发表时间：
1997-12-01
影响因子：
10.5
通讯作者：
Kingston, RE
中科院分区：
文献类型：
--
作者：
Brown, SA;Kingston, RE
转录延伸过程中的启动子-近端停顿是调节包括人类HSP70基因在内的许多不同位点的重要方式，染色质结构可以增强RNA聚合酶的停顿。我们证明，HSP70的激活导致RNA聚合酶前面转录的染色质的破坏。在体内，热休克后HSP70转录区域前400bp的染色质的破坏对转录抑制剂α-Amanitin具有抵抗力。进一步下游的染色质的破坏也发生在激活之后，但对α-Amanitin敏感，这表明需要聚合酶运动来破坏HSP70基因的远端部分。在体外，转录的染色质的破坏依赖于人类热休克因子1(HSF1)激活域的存在。这些实验证明，HSF1可以直接破坏转录区域的染色质。我们认为这是HSF1促进转录延长的机制之一。
Promoter-proximal pausing during transcriptional elongation is an important way of regulating many diverse loci, including tbe human hsp70 gene, Pausing of RNA polymerase can be enhanced by chromatin structure. We demonstrate that activation of hsp70 leads to disruption of transcribed chromatin in front of RNA polymerase. In vivo, disruption of chromatin in the first 400 bp of the transcribed region of hsp70 following heat shock is resistant to the transcriptional inhibitor alpha-amanitin. Disruption of chromatin farther downstream also occurs following activation but is sensitive to alpha-amanitin, suggesting that polymerase movement is needed to disrupt distal portions of the hsp70 gene. In vitro, disruption of transcribed chromatin is dependent on the presence of the human heat shock factor 1 (HSF1) activation domains. These experiments demonstrate that HSF1 can direct disruption of chromatin in transcribed regions. We suggest that this is one of the mechanisms used by HSF1 to facilitate transcriptional elongation.