GC skew defines distinct RNA polymerase pause sites in CpG island promoters.
GC skew defines distinct RNA polymerase pause sites in CpG island promoters.
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DOI：
10.1101/gr.189068.114
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发表时间：
2015-11
期刊：
影响因子：
7
通讯作者：
Vertino PM
中科院分区：
文献类型：
--
作者：
Kellner WA;Bell JS;Vertino PM
CpG 岛 (CGI) 与超过一半的人类基因启动子相关，其特点是独特的染色质环境和相对于周围基因组区域的高水平双向转录活性，表明 RNA 聚合酶 (Pol II) 越过 CGI 边界的进展受到限制。在这里，我们描述了一个新的转录调控步骤，其中 Pol II 遇到了与启动子近端暂停不同的额外延伸障碍，并且发生在 CGI 结构域的下游边界。对于大多数 CGI 相关启动子，Pol II 在启动子近端或远端位点表现出显性停顿，该停顿在位置和强度上都与高 GC 偏斜的局部区域相关，这是一种已知形成独特二级结构的序列特征。在信号诱导的基因激活后，显性暂停位点的长程增强子接触被选择性增强，这表明增强子在下游暂停位点的新作用。这些数据表明，与 DNA 序列和 CGI 结构域完整性相关的 CGI 相关基因子集的转录输出具有额外的控制水平。
CpG islands (CGIs) are associated with over half of human gene promoters and are characterized by a unique chromatin environment and high levels of bidirectional transcriptional activity relative to surrounding genomic regions, suggesting that RNA polymerase (Pol II) progression past the CGI boundaries is restricted. Here we describe a novel transcriptional regulatory step wherein Pol II encounters an additional barrier to elongation distinct from the promoter-proximal pause and occurring at the downstream boundary of the CGI domain. For most CGI-associated promoters, Pol II exhibits a dominant pause at either the promoter-proximal or this distal site that correlates, both in position and in intensity, with local regions of high GC skew, a sequence feature known to form unique secondary structures. Upon signal-induced gene activation, long-range enhancer contacts at the dominant pause site are selectively enhanced, suggesting a new role for enhancers at the downstream pause. These data point to an additional level of control over transcriptional output at a subset of CGI-associated genes that is linked to DNA sequence and the integrity of the CGI domain.