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-Structure paper
タイトル | Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L. |
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ジャーナル・号・ページ | Cell, Vol. 176, Issue 6, Page 1490-1501.e12, Year 2019 |
掲載日 | 2019年3月7日 |
著者 | Evan J Worden / Niklas A Hoffmann / Chad W Hicks / Cynthia Wolberger / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:30765112 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.96 - 3.9 Å |
構造データ | EMDB-0468, PDB-6nog: |
化合物 | ChemComp-SAM: |
由来 |
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キーワード | STRUCTURAL PROTEIN/TRANSFERASE/DNA / Ubiquitin / Nucleosome / Methyltransferase / STRUCTURAL PROTEIN-TRANSFERASE-DNA complex |