FACT caught in the act of manipulating the nucleosome

doi:10.1038/s41586-019-1820-0

GSTDTAP > 地球科学

DOI	10.1038/s41586-019-1820-0
	FACT caught in the act of manipulating the nucleosome
	Shen, Helen
	2020-05-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	577 期号:7790 页码:426-+
文章类型	Article
语种	英语
国家	USA
英文关键词	The organization of genomic DNA into nucleosomes profoundly affects all DNA-related processes in eukaryotes. The histone chaperone known as ' facilitates chromatin transcription' (FACT(1)) (consisting of subunits SPT16 and SSRP1) promotes both disassembly and reassembly of nucleosomes during gene transcription, DNA replication and DNA repair(2). However, the mechanism by which FACT causes these opposing outcomes is unknown. Here we report two cryo-electron-microscopic structures of human FACT in complex with partially assembled subnucleosomes, with supporting biochemical and hydrogen-deuterium exchange data. We find that FACT is engaged in extensive interactions with nucleosomal DNA and all histone variants. The large DNA-binding surface on FACT appears to be protected by the carboxy-terminal domains of both of its subunits, and this inhibition is released by interaction with H2A-H2B, allowing FACT-H2A-H2B to dock onto a complex containing DNA and histones H3 and H4 (ref. (3)). SPT16 binds nucleosomal DNA and tethers H2A-H2B through its carboxy-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 H2A-H2B dimer is present. Our data suggest a compelling mechanism for how FACT maintains chromatin integrity during polymerase passage, by facilitating removal of the H2A-H2B dimer, stabilizing intermediate subnucleosomal 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.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000509570100043
WOS关键词	BEAM-INDUCED MOTION ; CRYO-EM ; BAYESIAN-APPROACH ; STRUCTURAL BASIS ; PARTICLE ; TRANSCRIPTION ; H2A-H2B ; ORIENTATION ; SPOTITON ; FEATURES
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计	被引频次：151[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/280944
专题	地球科学资源环境科学气候变化
推荐引用方式 GB/T 7714	Shen, Helen. FACT caught in the act of manipulating the nucleosome[J]. NATURE,2020,577(7790):426-+.
APA	Shen, Helen.(2020).FACT caught in the act of manipulating the nucleosome.NATURE,577(7790),426-+.
MLA	Shen, Helen."FACT caught in the act of manipulating the nucleosome".NATURE 577.7790(2020):426-+.