Human promoters are intrinsically directional.
Human promoters are intrinsically directional.
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DOI：
10.1016/j.molcel.2014.12.029
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发表时间：
2015-02-19
期刊：
影响因子：
16
通讯作者：
Ohler U
中科院分区：
文献类型：
--
作者：
Duttke SHC;Lacadie SA;Ibrahim MM;Glass CK;Corcoran DL;Benner C;Heinz S;Kadonaga JT;Ohler U
发散转录，其中反向转录发生在真核生物启动子上游无注释基因的区域，已被认为是活性启动子的一般特性。在这里，我们表明人类基础RNA聚合酶II转录机制和核心启动子本质上是单向的，而反向转录物起源于它们自己同源的反向核心启动子。体外转录分析和细胞新生转录物图谱显示，反向起始位点的序列与正向起始位点的序列相似。使用DNase I可及性来定义近端启动子边界显示，多达一半的启动子是单向的，并且单向启动子在反向核心启动子序列的上游边缘及其相关的染色质特征上被耗尽。因此，分化转录不是转录过程的固有特性，而是正向和反向核心启动子存在的结果。
Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional, and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in cells revealed that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that up to half of promoters are unidirectional and that unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process, but rather the consequence of the presence of both forward- and reverse-directed core promoters.
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