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TitleMechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L.
Journal, issue, pagesCell, Vol. 176, Issue 6, Page 1490-1501.e12, Year 2019
Publish dateMar 7, 2019
AuthorsEvan J Worden / Niklas A Hoffmann / Chad W Hicks / Cynthia Wolberger /
PubMed AbstractMethylation 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.
External linksPubMed:30765112 / Publisher's page
KeywordsSTRUCTURAL PROTEIN/TRANSFERASE/DNA / Ubiquitin / Nucleosome / Methyltransferase / STRUCTURAL PROTEIN-TRANSFERASE-DNA complex
MethodsEM (single particle)
Resolution2.96 - 3.9 A
Structure data

EMDB-9384:
Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 2-to-1 complex

EMDB-0468:
Poised-state Dot1L bound to the H2B-Ubiquitinated nucleosome

EMDB-0480:
Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 1-to-1 complex

PDB-6nj9:
Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 2-to-1 complex

PDB-6nog:
Poised-state Dot1L bound to the H2B-Ubiquitinated nucleosome

PDB-6nqa:
Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 1-to-1 complex

Chemicals

ChemComp-SAM:
S-ADENOSYLMETHIONINES-Adenosyl methionine

Source
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)

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