Histone H3K79 methylation by DOT1L promotes Aurora B localization at centromeres in mitosis

作者全名："Yang, Dan; He, Yanji; Li, Renyan; Huang, Zhenting; Zhou, Yong; Shi, Yingxu; Deng, Zhongliang; Wu, Jingxian; Gao, Yanfei"

作者地址："[Huang, Zhenting; Wu, Jingxian; Gao, Yanfei] Chongqing Med Univ, Ctr Med Epigenet, Sch Basic Med Sci, Chongqing 400016, Peoples R China; [Yang, Dan; He, Yanji; Zhou, Yong; Shi, Yingxu; Deng, Zhongliang] Chongqing Med Univ, Affiliated Hosp 2, Chongqing 400016, Peoples R China; [Li, Renyan] Chongqing Populat & Family Planning Sci & Technol, Chongqing 401120, Peoples R China"

通信作者："Gao, YF (通讯作者)，Chongqing Med Univ, Ctr Med Epigenet, Sch Basic Med Sci, Chongqing 400016, Peoples R China."

来源：CELL REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001047766300001

JCR分区：Q1

影响因子：7.5

年份：2023

卷号：42

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Centromere localization of the chromosome passenger complex (CPC) is paramount for achieving accurate sister chromosome segregation in mitosis. Although it has been widely recognized that the recruitment of CPC is directly regulated by two histone codes, phosphorylation of histone H3 at threonine 3 (H3T3ph) and phosphorylation of histone H2A at threonine 120 (H2AT120ph), the regulation of CPC localization by other histone codes remains elusive. We show that dysfunction of disruptor of telomeric silencing 1 like (DOT1L) leads to mislocation of the CPC in prometaphase, caused by disturbing the level of H3T3ph and its reader Survivin. This cascade is initiated by over-dephosphorylation of H3T3ph mediated by the phosphatase RepoMan-PP1, whose scaffold RepoMan translocalizes to chromosomes, while the level of H3K79me2/3 is diminished. Together, our findings uncover a biological function of DOT1L and H3K79 methylation in mitosis and give insight into how genomic stability is coordinated by different histone codes."

基金机构："National Natural Science Foundation of China [31870768, 32071295]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0756]"

基金资助正文："We thank Chang -Young Jang and Yong Kee Kim (Sookmyung Women's University) for technical assistance and Xia Zhang (Molecular Medicine and Cancer Research Center, ChongQing Medical University) for assistance with fluorescence microscopy. This study was supported by the National Natural Science Foundation of China (grant nos. 31870768 and 32071295) and the Natural Science Foundation of Chongqing (grant no. CSTB2022NSCQ-MSX0756) ."