6PZV

Crystal Structure of Bovine DNMT1 RFTS domain in complex with H3K9me3 and Ubiquitin

6PZV の概要

• エントリーDOI: 10.2210/pdb6pzv/pdb
• 分子名称: Ubiquitin, DNA (cytosine-5)-methyltransferase 1, Histone H3.3, ... (6 entities in total)
• 機能のキーワード: dna methylation, dna methyltransferase 1, histone modification, ubiquitylation, dna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 96785.46

構造登録者

Ren, W.,Song, J. (登録日: 2019-08-01, 公開日: 2020-07-15, 最終更新日: 2025-04-02)

主引用文献

Ren, W.,Fan, H.,Grimm, S.A.,Guo, Y.,Kim, J.J.,Yin, J.,Li, L.,Petell, C.J.,Tan, X.F.,Zhang, Z.M.,Coan, J.P.,Gao, L.,Cai, L.,Detrick, B.,Cetin, B.,Cui, Q.,Strahl, B.D.,Gozani, O.,Wang, Y.,Miller, K.M.,O'Leary, S.E.,Wade, P.A.,Patel, D.J.,Wang, G.G.,Song, J.
Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation.
Proc.Natl.Acad.Sci.USA, 117:18439-18447, 2020

PubMed Abstract: In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.

PubMed: 32675241
DOI: 10.1073/pnas.2009316117

実験手法

X-RAY DIFFRACTION (3.01 Å)