The SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B

doi:10.1038/s41467-024-48418-7

	The SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B
	Sun, Wenqi 1,2; Dong, Qianhua 3; Li, Xueqing 1,2; Gao, Jinxin 3; Ye, Xianwen2,4 ; Hu, Chunyi 5; Li, Fei 3; Chen, Yong1,2,4
	2024-05-21
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	15 期号:1
发表状态	已发表
DOI	10.1038/s41467-024-48418-7
摘要	["Heterochromatin is generally associated with the nuclear periphery, but how the spatial organization of heterochromatin is regulated to ensure epigenetic silencing remains unclear. Here we found that Sad1, an inner nuclear membrane SUN-family protein in fission yeast, interacts with histone H2A-H2B but not H3-H4. We solved the crystal structure of the histone binding motif (HBM) of Sad1 in complex with H2A-H2B, revealing the intimate contacts between Sad1HBM and H2A-H2B. Structure-based mutagenesis studies revealed that the H2A-H2B-binding activity of Sad1 is required for the dynamic distribution of Sad1 throughout the nuclear envelope (NE). The Sad1-H2A-H2B complex mediates tethering telomeres and the mating-type locus to the NE. This complex is also important for heterochromatin silencing. Mechanistically, H2A-H2B enhances the interaction between Sad1 and HDACs, including Clr3 and Sir2, to maintain epigenetic identity of heterochromatin. Interestingly, our results suggest that Sad1 exhibits the histone-enhanced liquid-liquid phase separation property, which helps recruit heterochromatin factors to the NE. Our results uncover an unexpected role of SUN-family proteins in heterochromatin regulation and suggest a nucleosome-independent role of H2A-H2B in regulating Sad1's functionality.","Here authors identify the interaction between the SUN-family protein Sad1 and histone H2A-H2B in S. pombe, and reveal the roles of the Sad1-histone interaction in the association of heterochromatin with the nuclear envelope and heterochromatin silencing."]
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收录类别	SCI
语种	英语
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDB37010303] ; Shanghai Pilot Program for Basic Research - Chinese Academy of Science, Shanghai Branch[JCYJ-SHFY-2022-008] ; National Natural Science Foundation of China[31970576] ; NIH[R35GM134920-01] ; NSF[MCB-1934628]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001228997200030
出版者	NATURE PORTFOLIO
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/395914
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_陈勇组生命科学与技术学院_硕士生
通讯作者	Li, Fei; Chen, Yong
作者单位	1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Key Lab Epigenet Regulat &, Shanghai 201210, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.NYU, Dept Biol, New York, NY 10012 USA 4.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 5.Natl Univ Singapore, Fac Sci, Dept Biol Sci, Singapore, Singapore
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Sun, Wenqi,Dong, Qianhua,Li, Xueqing,et al. The SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B[J]. NATURE COMMUNICATIONS,2024,15(1).
APA	Sun, Wenqi.,Dong, Qianhua.,Li, Xueqing.,Gao, Jinxin.,Ye, Xianwen.,...&Chen, Yong.(2024).The SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B.NATURE COMMUNICATIONS,15(1).
MLA	Sun, Wenqi,et al."The SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B".NATURE COMMUNICATIONS 15.1(2024).