6PZV

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

Summary for 6PZV

• Entry DOI: 10.2210/pdb6pzv/pdb
• Descriptor: Ubiquitin, DNA (cytosine-5)-methyltransferase 1, Histone H3.3, ... (6 entities in total)
• Functional Keywords: dna methylation, dna methyltransferase 1, histone modification, ubiquitylation, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 96785.46

Authors

Ren, W.,Song, J. (deposition date: 2019-08-01, release date: 2020-07-15, Last modification date: 2025-04-02)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.01 Å)