RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Science. 2019 Feb 15;363(6428):744-747. doi: 10.1126/science.aav8912. Epub 2019 Feb 7.
RNA polymerase II (RNAPII) transcribes chromosomal DNA that contains multiple nucleosomes. The nucleosome forms transcriptional barriers, and nucleosomal transcription requires several additional factors in vivo. We demonstrate that the transcription elongation factors Elf1 and Spt4/5 cooperatively lower the barriers and increase the RNAPII processivity in the nucleosome. The cryo-electron microscopy structures of the nucleosome-transcribing RNAPII elongation complexes (ECs) reveal that Elf1 and Spt4/5 reshape the EC downstream edge and intervene between RNAPII and the nucleosome. They facilitate RNAPII progression through superhelical location SHL(-1) by adjusting the nucleosome in favor of the forward progression. They suppress pausing at SHL(-5) by preventing the stable RNAPII-nucleosome interaction. Thus, the EC overcomes the nucleosomal barriers while providing a platform for various chromatin functions.
RNA 聚合酶 II（RNAPII）转录包含多个核小体的染色体 DNA。核小体形成转录障碍，核小体转录需要体内的几个额外因子。我们证明转录延伸因子 Elf1 和 Spt4/5 协同降低障碍并增加核小体中 RNAPII 的延伸性。核小体转录的 RNAPII 延伸复合物（EC）的低温电子显微镜结构显示，Elf1 和 Spt4/5 重塑 EC 的下游边缘并干预 RNAPII 和核小体之间。它们通过调整核小体有利于向前推进，促进 RNAPII 通过超螺旋位置 SHL(-1)的进展。它们通过防止稳定的 RNAPII-核小体相互作用来抑制在 SHL(-5)处的暂停。因此，EC 克服了核小体障碍，同时为各种染色质功能提供了一个平台。
