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

被引：136

作者：

Ferry, Laure ^{[1
]}

Fournier, Alexandra ^{[1
]}

Tsusaka, Takeshi ^{[2
,3
]}

Adelmant, Guillaume ^{[4
]}

Shimazu, Tadahiro ^{[2
]}

Matano, Shohei ^{[5
]}

Kirsh, Olivier ^{[1
]}

Amouroux, Rachel ^{[6
,7
]}

Dohmae, Naoshi ^{[8
]}

Suzuki, Takehiro ^{[8
]}

Filion, Guillaume J. ^{[9
,10
]}

Deng, Wen ^{[11
,12
]}

de Dieuleveult, Maud ^{[1
]}

Fritsch, Lauriane ^{[1
,14
]}

Kudithipudi, Srikanth ^{[13
]}

Jeltsch, Albert ^{[13
]}

Leonhardt, Heinrich ^{[11
,12
]}

Hajkova, Petra ^{[6
,7
]}

Marto, Jarrod A. ^{[4
]}

Arita, Kyohei ^{[5
]}

Shinkai, Yoichi ^{[2
]}

Defossez, Pierre-Antoine ^{[1
]}

机构：

[1] Univ Paris Diderot, Sorbonne Paris Cite, Epigenet & Cell Fate, CNRS,UMR 7216, F-75013 Paris, France

[2] RIKEN Wako, Cellular Memory Lab, Wako, Saitama 3510198, Japan

[3] Kyoto Univ, Grad Sch Med Diabet Endocrinol & Nutr, Kyoto 6068507, Japan

[4] Harvard Med Sch, Blais Prote Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA

[5] Yokohama City Univ, Dept Med Life Sci, Yokohama, Kanagawa 2300045, Japan

[6] MRC, CSC, Du Cane Rd, London W12 0NN, England

[7] Imperial Coll London, ICS, Fac Med, Du Cane Rd, London W12 0NN, England

[8] RIKEN, Biomol Characterizat Unit, Ctr Sustainable Resource Sci, Wako, Saitama 3510198, Japan

[9] Barcelona Inst Sci & Technol, CRG, Barcelona 08003, Spain

[10] UPF, Barcelona 08002, Spain

[11] Ludwig Maximilians Univ Munchen, Dept Biol 2, D-82152 Planegg Martinsried, Germany

[12] Ludwig Maximilians Univ Munchen, CIPSM, D-82152 Planegg Martinsried, Germany

[13] Stuttgart Univ, Inst Biochem, D-70569 Stuttgart, Germany

[14] CNRS, UPR 1142, F-34090 Montpellier, France

来源：

MOLECULAR CELL | 2017年 / 67卷 / 04期

基金：

英国医学研究理事会; 欧洲研究理事会;

关键词：

LYSINE METHYLTRANSFERASE G9A; HISTONE METHYLTRANSFERASE; EPIGENETIC INHERITANCE; DNMT1; PROTEIN; MAINTENANCE; H3K9; STABILITY; NP95; DEUBIQUITINATION;

D O I：

10.1016/j.molcel.2017.07.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：550 / +

页数：21

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