Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation.

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Title: Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation.
Author(s): Ferry, L
Fournier, A
Tsusaka, T
Adelmant, G
Shimazu, T
Matano, S
Kirsh, O
Amouroux, R
Dohmae, N
Suzuki, T
Filion, GJ
Deng, W
De Dieuleveult, M
Fritsch, L
Kudithipudi, S
Jeltsch, A
Leonhardt, H
Hajkova, P
Marto, JA
Arita, K
Shinkai, Y
Defossez, P-A
Item 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.
Publication Date: 17-Aug-2017
Date of Acceptance: 10-Jul-2017
URI: http://hdl.handle.net/10044/1/50094
DOI: https://dx.doi.org/10.1016/j.molcel.2017.07.012
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/Funder: Commission of the European Communities
EMBO
Commission of the European Communities
Commission of the European Communities
Funder's Grant Number: 257082
EMBO YIP
274206
648879
Keywords: DNA methylation
DNA replication
G9a(Ehmt2)/GLP(Ehmt1)
UHRF1
epigenetics
lysine methylation
DNA methylation
DNA replication
G9a(Ehmt2)/GLP(Ehmt1)
UHRF1
epigenetics
lysine methylation
06 Biological Sciences
11 Medical And Health Sciences
Developmental Biology
Publication Status: Published
Conference Place: United States
Embargo Date: 2018-08-10
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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