小柯机器人

组蛋白伴侣FACT操控核小体
2019-11-28 13:55

美国科罗拉多大学博尔德分校Karolin Luger研究团队,探究了组蛋白伴侣“促染色质转录”复合体(FACT)如何操控核小体。该项研究成果在线发表在2019年11月27日的《自然》上。

研究人员通过辅助性的生化和氢氘交换(HDX)数据,解析了人FACT的两个冷冻电镜结构,其具有部分组装的亚核小体。FACT与核小体DNA和所有组蛋白进行广泛的相互作用。FACT的大DNA结合表面似乎受两个亚基C末端结构域的保护,并且这种抑制作用通过与H2A–H2B相互作用而释放,从而使FACT–H2A–H2B停靠在(H3–H4)2–DNA复合体上。SPT16通过其C末端结构域结合核小体DNA和固定H2A–H2B,发挥了DNA占位作用。SSRP1被认为通过两种构象帮助DNA结合,其构象取决于是否存在第二个H2A–H2B二聚体。该研究提出了一种令人信服的机制,这种机制解释了FACT如何通过促进H2A–H2B二聚体去除,稳定中间“亚核小体”状态并促进核小体重组来维持染色质完整性。研究人员的发现协调了关于FACT许多作用的差异,并强调了组蛋白伴侣和核小体之间的动态相互作用。

据悉,将基因组DNA包裹进核小体影响了真核生物中所有与DNA相关的过程。组蛋白伴侣FACT(由SPT16和SSRP11亚基组成)在基因转录、DNA复制和修复过程中促进核小体的解体和重组。然而,尚不清楚FACT介导的这种相反过程的机制。

附:英文原文

Title: FACT caught in the act of manipulating the nucleosome

Author: Yang Liu, Keda Zhou, Naifu Zhang, Hui Wei, Yong Zi Tan, Zhening Zhang, Bridget Carragher, Clinton S. Potter, Sheena DArcy, Karolin Luger

Issue&Volume: 2019-11-27

Abstract: The organization of genomic DNA into nucleosomes profoundly affects all DNA-related processes in eukaryotes. The histone chaperone FAcilitates Chromatin Transcription (FACT; consisting of subunits SPT16 and SSRP11) promotes both disassembly and reassembly of nucleosomes during gene transcription, DNA replication, and repair2. The mechanism by which FACT causes these opposing outcomes is unknown. Here we report two cryo-EM structures of human FACT in complex with partially assembled sub-nucleosomes, with supporting biochemical and hydrogendeuterium exchange (HDX) data. FACT is engaged in extensive interactions with nucleosomal DNA and all histones. The large DNA-binding surface on FACT appears to be protected by the C-terminal domains of both subunits, and this inhibition is released by interaction with H2AH2B, allowing FACTH2AH2B to dock onto a (H3H4)2DNA complex3. SPT16 binds nucleosomal DNA and tethers H2AH2B through its C-terminal domain by acting as a placeholder for DNA. SSRP1 also contributes to DNA binding, and can assume two conformations, depending on whether a second H2AH2B dimer is present. Our data suggest a compelling mechanism for how FACT maintains chromatin integrity during polymerase passage, by facilitating H2AH2B dimer removal, stabilizing intermediate sub-nucleosomal states, and promoting nucleosome reassembly. Our findings reconcile discrepancies regarding the many roles of FACT and underscore the dynamic interactions between histone chaperones and nucleosomes.

DOI: 10.1038/s41586-019-1820-0

Source:https://www.nature.com/articles/s41586-019-1820-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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