National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM095822
米国
引用
ジャーナル: Cell / 年: 2019 タイトル: Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L. 著者: Evan J Worden / Niklas A Hoffmann / Chad W Hicks / Cynthia Wolberger / 要旨: Methylation of histone H3 K79 by Dot1L is a hallmark of actively transcribed genes that depends on monoubiquitination of H2B K120 (H2B-Ub) and is an example of histone modification cross-talk that is ...Methylation of histone H3 K79 by Dot1L is a hallmark of actively transcribed genes that depends on monoubiquitination of H2B K120 (H2B-Ub) and is an example of histone modification cross-talk that is conserved from yeast to humans. We report here cryo-EM structures of Dot1L bound to ubiquitinated nucleosome that show how H2B-Ub stimulates Dot1L activity and reveal a role for the histone H4 tail in positioning Dot1L. We find that contacts mediated by Dot1L and the H4 tail induce a conformational change in the globular core of histone H3 that reorients K79 from an inaccessible position, thus enabling this side chain to insert into the active site in a position primed for catalysis. Our study provides a comprehensive mechanism of cross-talk between histone ubiquitination and methylation and reveals structural plasticity in histones that makes it possible for histone-modifying enzymes to access residues within the nucleosome core.
全体 : Poised state Dot1L in complex with the H2B-Ub nucleosome
全体
名称: Poised state Dot1L in complex with the H2B-Ub nucleosome
要素
複合体: Poised state Dot1L in complex with the H2B-Ub nucleosome
複合体: Dot1L
タンパク質・ペプチド: Histone-lysine N-methyltransferase, H3 lysine-79 specific
複合体: H2B-Ub nucleosome
複合体: histone core
タンパク質・ペプチド: Histone H3.2
タンパク質・ペプチド: Histone H4
タンパク質・ペプチド: Histone H2A type 1
タンパク質・ペプチド: Histone H2B 1.1
複合体: ubiquitin
タンパク質・ペプチド: Ubiquitin
複合体: DNA
DNA: 601 DNA Strand 1
DNA: 601 DNA Strand 2
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超分子 #1: Poised state Dot1L in complex with the H2B-Ub nucleosome
超分子
名称: Poised state Dot1L in complex with the H2B-Ub nucleosome タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all / 詳細: 1:1 complex of Dot1L bound to the nucleosome