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

Proceedings of the National Academy of Sciences of the United States of America
Wendan RenJikui Song

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.

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Citations

Aug 19, 2020·Essays in Biochemistry·Anusha SriramanKyle M Miller
Dec 15, 2020·Trends in Biochemical Sciences·Robert M VaughanScott B Rothbart
Mar 28, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xuan MingYingfeng Li
May 5, 2021·Nature Communications·Wendan RenJikui Song
May 21, 2021·Communications Biology·Julia FranzenWolfgang Wagner
Jun 19, 2021·Nature Structural & Molecular Biology·Chuck HaggertyAlexander Meissner
Oct 6, 2021·Nature Reviews. Genetics·Sanne M Janssen, Matthew C Lorincz

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