Author:
Jang Seongmin,Kang Chanshin,Yang Han-Sol,Jung Taeyang,Hebert Hans,Chung Ka Young,Kim Seung Joong,Hohng Sungchul,Song Ji-Joon
Abstract
DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.
Funder
National Research Foundation
Swedish Research Council
Global Science Experimental Data Hub Center
Korea Institute of Science and Technology Information
Korea National Research Foundation
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
68 articles.
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