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. 2017 Aug 17;67(4):550-565.e5.
doi: 10.1016/j.molcel.2017.07.012. Epub 2017 Aug 10.

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

Laure Ferry  1 , Alexandra Fournier  1 , Takeshi Tsusaka  2 , Guillaume Adelmant  3 , Tadahiro Shimazu  4 , Shohei Matano  5 , Olivier Kirsh  1 , Rachel Amouroux  6 , Naoshi Dohmae  7 , Takehiro Suzuki  7 , Guillaume J Filion  8 , Wen Deng  9 , Maud de Dieuleveult  1 , Lauriane Fritsch  1 , Srikanth Kudithipudi  10 , Albert Jeltsch  10 , Heinrich Leonhardt  9 , Petra Hajkova  6 , Jarrod A Marto  3 , Kyohei Arita  5 , Yoichi Shinkai  11 , Pierre-Antoine Defossez  12
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Free article

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

Laure Ferry et al. Mol Cell. .
Free 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.

Keywords: DNA methylation; DNA replication; G9a(Ehmt2)/GLP(Ehmt1); UHRF1; epigenetics; lysine methylation.

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