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TitleStructural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase.
Journal, issue, pagesGenes Dev, Vol. 33, Issue 11-12, Page 620-625, Year 2019
Publish dateJun 1, 2019
AuthorsSeongmin Jang / Chanshin Kang / Han-Sol Yang / Taeyang Jung / Hans Hebert / Ka Young Chung / Seung Joong Kim / Sungchul Hohng / Ji-Joon Song /
PubMed AbstractDOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we ...DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.
External linksGenes Dev / PubMed:30923167 / PubMed Central
MethodsEM (single particle)
Resolution6.8 - 7.3 Å
Structure data

EMDB-9843, PDB-6jm9:
cryo-EM structure of DOT1L bound to unmodified nucleosome
Method: EM (single particle) / Resolution: 7.3 Å

EMDB-9844, PDB-6jma:
cryo-EM structure of DOT1L bound to H2B ubiquitinated nucleosome
Method: EM (single particle) / Resolution: 6.8 Å

Chemicals

ChemComp-SAM:
S-ADENOSYLMETHIONINE / S-Adenosyl methionine

Source
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
  • homo sapiens (human)
KeywordsGENE REGULATION / histone / nucleosome / methylation

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