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-Structure paper
タイトル | Nucleosome and ubiquitin position Set2 to methylate H3K36. |
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ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 3795, Year 2019 |
掲載日 | 2019年8月22日 |
著者 | Silvija Bilokapic / Mario Halic / |
PubMed 要旨 | Histone H3 lysine 36 methylation (H3K36me) is a conserved histone modification deposited by the Set2 methyltransferases. Recent findings show that over-expression or mutation of Set2 enzymes promotes ...Histone H3 lysine 36 methylation (H3K36me) is a conserved histone modification deposited by the Set2 methyltransferases. Recent findings show that over-expression or mutation of Set2 enzymes promotes cancer progression, however, mechanisms of H3K36me are poorly understood. Set2 enzymes show spurious activity on histones and histone tails, and it is unknown how they obtain specificity to methylate H3K36 on the nucleosome. In this study, we present 3.8 Å cryo-EM structure of Set2 bound to the mimic of H2B ubiquitinated nucleosome. Our structure shows that Set2 makes extensive interactions with the H3 αN, the H3 tail, the H2A C-terminal tail and stabilizes DNA in the unwrapped conformation, which positions Set2 to specifically methylate H3K36. Moreover, we show that ubiquitin contributes to Set2 positioning on the nucleosome and stimulates the methyltransferase activity. Notably, our structure uncovers interfaces that can be targeted by small molecules for development of future cancer therapies. |
リンク | Nat Commun / PubMed:31439846 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.3 - 4.1 Å |
構造データ | EMDB-20516, PDB-6px1: EMDB-20517, PDB-6px3: |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | GENE REGULATION / Set2 / nucleosome / chromatin / KMT |