Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, United States.
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, United States.
J Mol Biol. 2021 Jul 9;433(14):166979. doi: 10.1016/j.jmb.2021.166979. Epub 2021 Apr 1.
The regulation of transcription by RNA polymerase II is closely intertwined with the regulation of chromatin structure. A host of proteins required for the disassembly, reassembly, and modification of nucleosomes interacts with Pol II to aid its movement and counteract its disruptive effects on chromatin. The highly conserved Polymerase Associated Factor 1 Complex, Paf1C, travels with Pol II and exerts control over transcription elongation and chromatin structure, while broadly impacting the transcriptome in both single cell and multicellular eukaryotes. Recent studies have yielded exciting new insights into the mechanisms by which Paf1C regulates transcription elongation, epigenetic modifications, and post-transcriptional steps in eukaryotic gene expression. Importantly, these functional studies are now supported by an extensive foundation of high-resolution structural information, providing intimate views of Paf1C and its integration into the larger Pol II elongation complex. As a global regulatory factor operating at the interface between chromatin and transcription, the impact of Paf1C is broad and its influence reverberates into other domains of nuclear regulation, including genome stability, telomere maintenance, and DNA replication.
RNA 聚合酶 II 的转录调控与染色质结构的调控密切交织在一起。许多解聚、重新组装和修饰核小体所需的蛋白质与 Pol II 相互作用,以帮助其运动并抵消其对染色质的破坏作用。高度保守的聚合酶相关因子 1 复合物(Paf1C)与 Pol II 一起移动,并对转录延伸和染色质结构进行控制,同时在单细胞和多细胞真核生物中广泛影响转录组。最近的研究为 Paf1C 调节转录延伸、表观遗传修饰以及真核基因表达中的转录后步骤的机制提供了令人兴奋的新见解。重要的是,这些功能研究现在得到了广泛的高分辨率结构信息基础的支持,提供了 Paf1C 及其与更大的 Pol II 延伸复合物的整合的详细视图。作为一个在染色质和转录之间的界面上发挥全局调节作用的因子,Paf1C 的影响广泛,其影响回荡到核调节的其他领域,包括基因组稳定性、端粒维持和 DNA 复制。