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.

中文翻译：

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PAF1通过增强子激活调节启动子-近端暂停释放

后生动物中的基因表达受RNA聚合酶II（Pol II）启动子附近的暂停及其释放的调控。先前，我们显示了Pol II相关因子1（PAF1）将暂停的Pol II的释放调节为有效的延伸。在这里，我们发现PAF1占据了转录增强子，并抑制了这些增强子的过度激活。PAF1丢失导致增强子激活，从附近PAF1靶基因的暂停启动子中释放Pol II。敲除PAF1调节的增强子可减弱PAF1靶基因上暂停的Pol II的释放，而不会对其关联的启动子建立停顿产生重大干扰。因此，增强子的一个子集可以通过以PAF1依赖的方式控制暂停的Pol II的释放来主要调节基因表达。