Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Science. 2022 Jun 17;376(6599):1313-1316. doi: 10.1126/science.abo3851. Epub 2022 Jun 16.
In eukaryotes, RNA polymerase (Pol) II transcribes chromatin and must move past nucleosomes, often resulting in nucleosome displacement. How Pol II unwraps the DNA from nucleosomes to allow transcription and how DNA rewraps to retain nucleosomes has been unclear. Here, we report the 3.0-angstrom cryo-electron microscopy structure of a mammalian Pol II-DSIF-SPT6-PAF1c-TFIIS-nucleosome complex stalled 54 base pairs within the nucleosome. The structure provides a mechanistic basis for nucleosome retention during transcription elongation where upstream DNA emerging from the Pol II cleft has rewrapped the proximal side of the nucleosome. The structure uncovers a direct role for Pol II and transcription elongation factors in nucleosome retention and explains how nucleosomes are retained to prevent the disruption of chromatin structure across actively transcribed genes.
在真核生物中,RNA 聚合酶(Pol)II 转录染色质,必须穿过核小体,这通常会导致核小体位移。Pol II 如何将 DNA 从核小体上解开以允许转录,以及 DNA 如何重新缠绕以保留核小体,这些问题一直不清楚。在这里,我们报告了哺乳动物 Pol II-DSIF-SPT6-PAF1c-TFIIS-核小体复合物的 3.0 埃冷冻电镜结构,该复合物在核小体中停滞在 54 个碱基对内。该结构为转录延伸过程中核小体保留提供了一个机械基础,其中从 Pol II 裂缝中出现的上游 DNA 已重新缠绕核小体的近端侧。该结构揭示了 Pol II 和转录延伸因子在核小体保留中的直接作用,并解释了如何保留核小体以防止在活跃转录的基因中破坏染色质结构。