Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L | Zendy

Evan J. Worden | Zendy; N. Hoffmann | Zendy; Chad W. Hicks | Zendy; Cynthia Wolberger | Zendy

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Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L

Author(s) -

Evan J. Worden,

N. Hoffmann,

Chad W. Hicks,

Cynthia Wolberger

Publication year - 2019

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2019.02.002

Subject(s) - biology , histone h3 , nucleosome , histone octamer , histone code , histone methylation , histone methyltransferase , histone , histone h2b , histone h2a , histone h1 , microbiology and biotechnology , genetics , dna methylation , dna , gene , gene expression

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.

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