Chen Fei Xavier, Xie Peng, Collings Clayton K, Cao Kaixiang, Aoi Yuki, Marshall Stacy A, Rendleman Emily J, Ugarenko Michal, Ozark Patrick A, Zhang Anda, Shiekhattar Ramin, Smith Edwin R, Zhang Michael Q, Shilatifard Ali
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Richardson, TX 75080, USA.
Science. 2017 Sep 22;357(6357):1294-1298. doi: 10.1126/science.aan3269. Epub 2017 Aug 31.
Gene expression in metazoans is regulated by RNA polymerase II (Pol II) promoter-proximal pausing and its release. Previously, we showed that Pol II-associated factor 1 (PAF1) modulates the release of paused Pol II into productive elongation. Here, we found that PAF1 occupies transcriptional enhancers and restrains hyperactivation of a subset of these enhancers. Enhancer activation as the result of PAF1 loss releases Pol II from paused promoters of nearby PAF1 target genes. Knockout of PAF1-regulated enhancers attenuates the release of paused Pol II on PAF1 target genes without major interference in the establishment of pausing at their cognate promoters. Thus, a subset of enhancers can primarily modulate gene expression by controlling the release of paused Pol II in a PAF1-dependent manner.
后生动物中的基因表达受RNA聚合酶II（Pol II）启动子近端暂停及其释放的调控。此前，我们发现Pol II相关因子1（PAF1）可调节暂停的Pol II向有效延伸的释放。在此，我们发现PAF1占据转录增强子并抑制其中一部分增强子的过度激活。PAF1缺失导致的增强子激活会使附近PAF1靶基因暂停启动子上的Pol II释放。敲除PAF1调控的增强子会减弱PAF1靶基因上暂停的Pol II的释放，而对其同源启动子处暂停的建立没有重大干扰。因此，一部分增强子可主要通过以PAF1依赖的方式控制暂停的Pol II的释放来调节基因表达。
