PAF1, a Molecular Regulator of Promoter-Proximal Pausing by RNA Polymerase II.
PAF1, a Molecular Regulator of Promoter-Proximal Pausing by RNA Polymerase II.
复制标题
DOI：
10.1016/j.cell.2015.07.042
复制
发表时间：
2015-08-27
期刊：
影响因子：
64.5
通讯作者：
Shilatifard A
中科院分区：
文献类型：
--
作者：
Chen FX;Woodfin AR;Gardini A;Rickels RA;Marshall SA;Smith ER;Shiekhattar R;Shilatifard A
启动子近端暂停和RNA聚合酶II（Pol II）的释放的控制是一种广泛使用的机制，用于调节后生动物的基因表达，特别是对环境和发育线索的基因。在这里，我们确定Pol II相关因子1（PAF 1）具有进化上保守的功能，在后生动物的调节启动子近端暂停。PAF 1水平的降低导致暂停的Pol II释放到数千个基因的基因体中。PAF 1耗竭导致新生和成熟转录物增加以及Pol II的丝氨酸2（Ser 2 P）上的C-末端结构域的磷酸化水平增加。这些变化可以解释为Ser 2 P激酶超延长复合物（SEC）的招聘影响增加释放暂停Pol II到生产性延长，从而建立一个新的功能，PAF 1作为一个调节器的启动子近端暂停Pol II。
The control of promoter-proximal pausing and the release of RNA polymerase II (Pol II) is a widely used mechanism for regulating gene expression in metazoans, especially for genes that respond to environmental and developmental cues. Here, we identify Pol II-associated Factor 1 (PAF1) to possess an evolutionarily conserved function in metazoans in the regulation of promoter-proximal pausing. Reduction in PAF1 levels leads to an increased release of paused Pol II into gene bodies at thousands of genes. PAF1 depletion results in increased nascent and mature transcripts and increased levels of phosphorylation of Pol II’s C-terminal domain on serine 2 (Ser2P). These changes can be explained by the recruitment of the Ser2P kinase Super Elongation Complex (SEC) effecting increased release of paused Pol II into productive elongation, thus establishing a novel function for PAF1 as a regulator of promoter-proximal pausing by Pol II.