Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30765112.
- Also identified by DOI 10.1016/j.cell.2019.02.002 and PMC identifier 6498860.
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Abstract
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.
Medical subject headings
- Histone-Lysine N-Methyltransferase
- Histones