Methylation of DNA ligase 1 by G9a/GLP recruits UHRF1 to replicating DNA and regulates DNA methylation
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered. Here, we present evidence for a direct recruitment of UHRF1 by the replication machinery via DNA ligase 1 (LIG1). A histone H3K9-like mimic within LIG1 is methylated by G9a and GLP and, compared with H3K9me2/3, more avidly binds UHRF1. Interaction with methylated LIG1 promotes the recruitment of UHRF1 to DNA replication sites and is required for DNA methylation maintenance. These results further elucidate the function of UHRF1, identify a non-histone target of G9a and GLP, and provide an example of a histone mimic that coordinates DNA replication and DNA methylation maintenance.
Date Issued
2017-08-17
Date Acceptance
2017-07-10
Citation
Molecular Cell, 2017, 67 (4), pp.550-565.e5
ISSN
1097-2765
Publisher
Elsevier
Start Page
550
End Page
565.e5
Journal / Book Title
Molecular Cell
Volume
67
Issue
4
Copyright Statement
© 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Commission of the European Communities
EMBO
Commission of the European Communities
Commission of the European Communities
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/28803780
PII: S1097-2765(17)30506-3
Grant Number
257082
EMBO YIP
648879
274206
Subjects
DNA methylation
DNA replication
G9a(Ehmt2)/GLP(Ehmt1)
UHRF1
epigenetics
lysine methylation
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2017-08-10