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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 linksCell / PubMed:30765112 / PubMed Central
MethodsEM (single particle)
Resolution2.96 - 3.9 Å
Structure data

0468

6nog

EMDB-0468, PDB-6nog:
Poised-state Dot1L bound to the H2B-Ubiquitinated nucleosome
Method: EM (single particle) / Resolution: 3.9 Å

0480

6nqa

EMDB-0480, PDB-6nqa:
Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 1-to-1 complex
Method: EM (single particle) / Resolution: 3.54 Å

9384

6nj9

EMDB-9384, PDB-6nj9:
Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 2-to-1 complex
Method: EM (single particle) / Resolution: 2.96 Å

Chemicals

ChemComp-SAM:
S-ADENOSYLMETHIONINE

Source
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
KeywordsSTRUCTURAL PROTEIN/TRANSFERASE/DNA / Ubiquitin / Nucleosome / Methyltransferase / STRUCTURAL PROTEIN-TRANSFERASE-DNA complex

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