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

Laure Ferry; Alexandra Fournier; Takeshi Tsusaka; Guillaume Adelmant; Tadahiro Shimazu; Shohei Matano; Olivier Kirsh; Rachel Amouroux; Naoshi Dohmae; Takehiro Suzuki; Guillaume J. Filion; Wen Deng; Maud de Dieuleveult; Lauriane Fritsch; Srikanth Kudithipudi; Albert Jeltsch; Heinrich Leonhardt; Petra Hajkova; Jarrod A. Marto; Kyohei Arita; Yoichi Shinkai; Pierre Antoine Defossez

doi:10.1016/j.molcel.2017.07.012

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

Laure Ferry, Alexandra Fournier, Takeshi Tsusaka, Guillaume Adelmant, Tadahiro Shimazu, Shohei Matano, Olivier Kirsh, Rachel Amouroux, Naoshi Dohmae, Takehiro Suzuki, Guillaume J. Filion, Wen Deng, Maud de Dieuleveult, Lauriane Fritsch, Srikanth Kudithipudi, Albert Jeltsch, Heinrich Leonhardt, Petra Hajkova, Jarrod A. Marto, Kyohei AritaYoichi Shinkai, Pierre Antoine Defossez

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	550-565.e5
Journal	Molecular Cell
Volume	67
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2017.07.012
Publication status	Published - 17 Aug 2017
Externally published	Yes

Keywords

DNA methylation
DNA replication
G9a(Ehmt2)/GLP(Ehmt1)
UHRF1
epigenetics
lysine methylation

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10.1016/j.molcel.2017.07.012

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Ferry, L., Fournier, A., Tsusaka, T., Adelmant, G., Shimazu, T., Matano, S., Kirsh, O., Amouroux, R., Dohmae, N., Suzuki, T., Filion, G. J., Deng, W., de Dieuleveult, M., Fritsch, L., Kudithipudi, S., Jeltsch, A., Leonhardt, H., Hajkova, P., Marto, J. A., ... Defossez, P. A. (2017). Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation. Molecular Cell, 67(4), 550-565.e5. https://doi.org/10.1016/j.molcel.2017.07.012

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title = "Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation",

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",

author = "Laure Ferry and Alexandra Fournier and Takeshi Tsusaka and Guillaume Adelmant and Tadahiro Shimazu and Shohei Matano and Olivier Kirsh and Rachel Amouroux and Naoshi Dohmae and Takehiro Suzuki and Filion, \{Guillaume J.\} and Wen Deng and \{de Dieuleveult\}, Maud and Lauriane Fritsch and Srikanth Kudithipudi and Albert Jeltsch and Heinrich Leonhardt and Petra Hajkova and Marto, \{Jarrod A.\} and Kyohei Arita and Yoichi Shinkai and Defossez, \{Pierre Antoine\}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = aug,

day = "17",

doi = "10.1016/j.molcel.2017.07.012",

language = "English",

volume = "67",

pages = "550--565.e5",

journal = "Molecular Cell",

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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, PA 2017, 'Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation', Molecular Cell, vol. 67, no. 4, pp. 550-565.e5. https://doi.org/10.1016/j.molcel.2017.07.012

TY - JOUR

T1 - Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation

AU - Ferry, Laure

AU - Fournier, Alexandra

AU - Tsusaka, Takeshi

AU - Adelmant, Guillaume

AU - Shimazu, Tadahiro

AU - Matano, Shohei

AU - Kirsh, Olivier

AU - Amouroux, Rachel

AU - Dohmae, Naoshi

AU - Suzuki, Takehiro

AU - Filion, Guillaume J.

AU - Deng, Wen

AU - de Dieuleveult, Maud

AU - Fritsch, Lauriane

AU - Kudithipudi, Srikanth

AU - Jeltsch, Albert

AU - Leonhardt, Heinrich

AU - Hajkova, Petra

AU - Marto, Jarrod A.

AU - Arita, Kyohei

AU - Shinkai, Yoichi

AU - Defossez, Pierre Antoine

PY - 2017/8/17

Y1 - 2017/8/17

N2 - 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.

AB - 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.

KW - DNA methylation

KW - DNA replication

KW - G9a(Ehmt2)/GLP(Ehmt1)

KW - UHRF1

KW - epigenetics

KW - lysine methylation

U2 - 10.1016/j.molcel.2017.07.012

DO - 10.1016/j.molcel.2017.07.012

M3 - Article

C2 - 28803780

AN - SCOPUS:85027561015

SN - 1097-2765

VL - 67

SP - 550-565.e5

JO - Molecular Cell

JF - Molecular Cell

IS - 4

ER -

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

Abstract

Keywords

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