Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L.
- Resource Type
- Article
- Authors
- Worden, Evan J.; Hoffmann, Niklas A.; Hicks, Chad W.; Wolberger, Cynthia
- Source
- Cell. Mar2019, Vol. 176 Issue 6, p1490-1490. 1p.
- Subject
- *BIOLOGICAL crosstalk
*UBIQUITINATION
*HISTONE methylation
*CHROMATIN
*UBIQUITIN
- Language
- ISSN
- 0092-8674
Summary 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. Graphical Abstract Highlights • Cryo-EM structures of Dot1L methyltransferase bound to H2B-ubiquitinated nucleosomes • Dot1L bound in poised and active states contacts the ubiquitin I36 hydrophobic patch • The tail of histone H4 binds in a cleft in Dot1L. • A conformational change is induced in histone H3 that enables Dot1L to access H3K79 Unanticipated conformational plasticity in the globular core of histone H3 underlies cross-talk between histone modifications. [ABSTRACT FROM AUTHOR]