Structural basis of the crosstalk between histone H2B monoubiquitination and H3 lysine 79 methylation on nucleosome

摘要：

Dear Editor,Histone marks deposited by post-translational modifications (PTMs) frequently occur in interrelated combinational patterns to create a complex and precise control on the chromatin structure and function.1 One of the landmark findings of histone PTM crosstalk is the trans-histone regulation of histone H3 lysine 79 (H3K79) methylation by the monoubiquitination of histone H2B on lysine 120 (H2BK120).2Mono-,di-,and tri-methylation of histone H3K79 serves as a prominent histone mark that participates in transcription regulation and DNA damage response.3 H2BK120 monoubiquitination (H2BK120ub1) is a prerequisite for the efficient methylation of H3K79 by the unique non-SET domaincontaining histone methyltransferase DOT1L (Disrupter of telomere silencing protein 1-1ike) in vivo.2 Incorporation of chemically monoubiquitinated H2B into in vitro reconstituted nucleosome directly stimulates the catalytic activity of DOT1 L4 (Supplementary information,Figs.S1 and S2).It still remains poorly understood how the H3K79 methyl marks are deposited and how the associated PTM crosstalk occurs on nucleosome.

所属期刊栏目：29

资助基金：We thank staffs from the Electron Microscopy System and the Database and Computation System of the National Facility for Protein Science in Shanghai;Zhangjiang Lab for their assistance with the EM instruments and data pre-processing.We are grateful to the NFPS Large-scale Protein Preparation System and Mass Spectrometry System for instrument support and technical assistance.This work was supported by the National Key R&D Program of China2016YFA0501803 and 2017YFA0504504;the National Natural Science Foundation of China31570766 and U1632130;the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support2017YZ004;the SHIPM-sigma fund BJ1-7009-18-1303 and JY201805 from Shanghai Institute of Precision Medicine,Ninth People”s Hospital,Shanghai Jiao Tong University School of Medicine,and Chinese Academy of Sciences Facility-based Open Research Program.J.H.is a recipient of the Thousand Young Talents Program of

在线出版日期：2019-05-21（万方平台首次上网日期，不代表论文的发表时间）

页数：共4页

页码：330-333