Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation Journal Article

Authors: 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.; Çetin, 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.
Article Title: Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation
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. © 2020 National Academy of Sciences. All rights reserved.
Keywords: signal transduction; controlled study; nonhuman; protein domain; protein localization; animal cell; mouse; embryonic stem cell; dna methylation; enzyme regulation; ubiquitination; gene disruption; genomic instability; gene identification; dna binding; heterochromatin; mammal cell; allosteric regulation; gene replication; dnmt1; h3k9me3; human; priority journal; article; dna (cytosine 5) methyltransferase 1
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 117
Issue: 31
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2020-08-04
Start Page: 18439
End Page: 18447
Language: English
DOI: 10.1073/pnas.2009316117
PUBMED: 32675241
PROVIDER: scopus
PMCID: PMC7414182
Notes: Article -- Source: Scopus
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MSK Authors
  1. Dinshaw J Patel
    463 Patel