組蛋白伴侶FACT操控核小體
作者：
小柯機器人發布時間：2019/11/28 13:55:26
美國科羅拉多大學博爾德分校Karolin Luger研究團隊，探究了組蛋白伴侶「促染色質轉錄」複合體（FACT）如何操控核小體。該項研究成果在線發表在2019年11月27日的《自然》上。
研究人員通過輔助性的生化和氫氘交換（HDX）數據，解析了人FACT的兩個冷凍電鏡結構，其具有部分組裝的亞核小體。FACT與核小體DNA和所有組蛋白進行廣泛的相互作用。FACT的大DNA結合表面似乎受兩個亞基C末端結構域的保護，並且這種抑制作用通過與H2A–H2B相互作用而釋放，從而使FACT–H2A–H2B停靠在（H3–H4）2–DNA複合體上。SPT16通過其C末端結構域結合核小體DNA和固定H2A–H2B，發揮了DNA佔位作用。SSRP1被認為通過兩種構象幫助DNA結合，其構象取決於是否存在第二個H2A–H2B二聚體。該研究提出了一種令人信服的機制，這種機制解釋了FACT如何通過促進H2A–H2B二聚體去除，穩定中間「亞核小體」狀態並促進核小體重組來維持染色質完整性。研究人員的發現協調了關於FACT許多作用的差異，並強調了組蛋白伴侶和核小體之間的動態相互作用。
據悉，將基因組DNA包裹進核小體影響了真核生物中所有與DNA相關的過程。組蛋白伴侶FACT（由SPT16和SSRP11亞基組成）在基因轉錄、DNA複製和修復過程中促進核小體的解體和重組。然而，尚不清楚FACT介導的這種相反過程的機制。
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