| Literature DB >> 32675241 |
Wendan Ren1, Huitao Fan2,3, Sara A Grimm4, Yiran Guo2,3, Jae Jin Kim5, Jiekai Yin6, Linhui Li1, Christopher J Petell2,3, Xiao-Feng Tan1, Zhi-Min Zhang1, John P Coan7, Linfeng Gao6, Ling Cai2,3, Brittany Detrick1, Burak Çetin8, Qiang Cui9,10,11, Brian D Strahl2,3, Or Gozani7, Yinsheng Wang6,12, Kyle M Miller5, Seán E O'Leary1,8, Paul A Wade4, Dinshaw J Patel13, Gang Greg Wang14,3, Jikui Song15,6.
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.Entities:
Keywords: DNA methylation; DNMT1; H3K9me3; allosteric regulation
Mesh：
Substances：
Year: 2020 PMID： 32675241 PMCID： PMC7414182 DOI： 10.1073/pnas.2009316117
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 12.779