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

BioRxiv : the Preprint Server for Biology
W. RenJikui Song


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 ES cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly regulates DNMT1-mediated maintenance DNA methylation.

Related Concepts

Stress Fractures
Gene Therapy
Process Assessment (Health Care)
Biologist (General)
Gene Mutant
Population Group

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

Proceedings. Biological Sciences
Stephen R ProulxLocke Rowe
Canadian Family Physician Médecin De Famille Canadien
Donna Cherniak
© 2021 Meta ULC. All rights reserved