Functions of FACT in Breaking the Nucleosome and Maintaining Its Integrity at the Single-Nucleosome Level

被引:99
作者
Chen, Ping [1 ]
Dong, Liping [1 ,4 ]
Hu, Mingli [1 ,4 ]
Wang, Yi-Zhou [2 ,3 ,4 ]
Xiao, Xue [2 ,3 ,4 ]
Zhao, Zhongliang [1 ]
Yan, Jie [5 ,6 ]
Wang, Peng-Ye [2 ,3 ,4 ]
Reinberg, Danny [7 ]
Li, Ming [2 ,3 ,4 ]
Li, Wei [2 ,3 ]
Li, Guohong [1 ,4 ]
机构
[1] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing, Peoples R China
[2] Chinese Acad Sci, Inst Phys, Natl Lab Condensed Matter Phys, Beijing, Peoples R China
[3] Chinese Acad Sci, Inst Phys, Key Lab Soft Matter Phys, Beijing, Peoples R China
[4] Univ Chinese Acad Sci, Beijing, Peoples R China
[5] Natl Univ Singapore, Dept Phys, Singapore 117542, Singapore
[6] Natl Univ Singapore, Mechanobiol Inst, Singapore 117411, Singapore
[7] NYU, Langone Sch Med, Howard Hughes Med Inst, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA
基金
中国国家自然科学基金;
关键词
HISTONE-DNA INTERACTIONS; RNA-POLYMERASE-II; SIMIAN-VIRUS-40; CHROMOSOME; CRYSTAL-STRUCTURE; CHROMATIN; REPLICATION; TRANSCRIPTION; ELONGATION; DOMAIN; SSRP1;
D O I
10.1016/j.molcel.2018.06.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The human FACT (facilitates chromatin transcription) complex, composed of two subunits SPT16 (Suppressor of Ty 16) and SSRP1 (Structure-specific recognition protein-1), plays essential roles in nucleosome remodeling. However, the molecular mechanism of FACT reorganizing the nucleosome still remains elusive. In this study, we demonstrate that FACT displays dual functions in destabilizing the nucleosome and maintaining the original histones and nucleosome integrity at the single-nucleosome level. We found that the subunit SSRP1 is responsible for maintenance of nucleosome integrity by holding the H3/H4 tetramer on DNA and promoting the deposition of the H2A/H2B dimer onto the nucleosome. In contrast, the large subunit SPT16 destabilizes the nucleosome structure by displacing the H2A/H2B dimers. Our findings provide mechanistic insights by which the two subunits of FACT coordinate with each other to fulfill its functions and suggest that FACT may play essential roles in preserving the original histones with epigenetic identity during transcription or DNA replication.
引用
收藏
页码:284 / +
页数:14
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