美国哈佛医学院Lucas Farnung团队近期取得重要工作进展，他们研究发现了转录延伸过程中核小体保留的结构基础。相关论文2022年6月17日在线发表于《科学》杂志上。

在这里，研究人员报告了哺乳动物Pol II-DSIF-SPT6-PAF1c-TFIIS-核小体复合物的3.0埃低温电子显微镜结构在核小体内停滞了54个碱基对。该结构为转录延伸期间核小体保留提供了机械基础，其中从Pol II裂缝中出现的上游DNA重新包裹了核小体的近侧。 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染色质结构在活跃转录基因中被破坏。

据介绍，在真核生物中，RNA聚合酶(Pol) II转录染色质并且必须通过核小体，经常导致核小体移位。Pol II如何将DNA从核小体中解开以允许转录，以及DNA如何重新包裹以保留核小体还不清楚。

附：英文原文

Title: Structural basis of nucleosome retention during transcription elongation

Author: Martin Filipovski, Jelly H. M. Soffers, Seychelle M. Vos, Lucas Farnung

Issue&Volume: 2022-06-17

Abstract: 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.

DOI: abo3851

Source: https://www.science.org/doi/10.1126/science.abo3851