Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a

Rachel Deplus; Loïc Blanchon; Arumugam Rajavelu; Abdelhalim Boukaba; Matthieu Defrance; Judith Luciani; Françoise Rothé; Sarah Dedeurwaerder; Hélène Denis; Arie B. Brinkman; Femke Simmer; Fabian Müller; Benjamin Bertin; Maria Berdasco; Pascale Putmans; Emilie Calonne; David W. Litchfield; Yvan De Launoit; Tomasz P. Jurkowski; Hendrik G. Stunnenberg; Christoph Bock; Christos Sotiriou; Mario F. Fraga; Manel Esteller; Albert Jeltsch; François Fuks

doi:10.1016/j.celrep.2014.06.048

Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a

Rachel Deplus
, Loïc Blanchon
, Arumugam Rajavelu
, Abdelhalim Boukaba
, Matthieu Defrance
, Judith Luciani
, Françoise Rothé
, Sarah Dedeurwaerder
, Hélène Denis
, Arie B. Brinkman
, Femke Simmer
, Fabian Müller
, Benjamin Bertin
, Maria Berdasco
, Pascale Putmans
, Emilie Calonne
, David W. Litchfield
, Yvan De Launoit
, Tomasz P. Jurkowski
, Hendrik G. Stunnenberg

Christoph Bock, Christos Sotiriou, Mario F. Fraga, Manel Esteller, Albert Jeltsch, François Fuks

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

69 Citaten (Scopus)

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DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA methylation analysis shows that CK2 primarily modulates CpG methylation of several repeats, most notably of Alu SINEs. This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. By revealing phosphorylation as a mode of regulation of de novo DNA methyltransferase function and by uncovering a mechanism for the regulation of methylation at repetitive elements, our results shed light on the origin of DNA methylation patterns.

Originele taal-2	Engels
Pagina's (van-tot)	743-753
Aantal pagina's	11
Tijdschrift	Cell reports
Volume	8
Nummer van het tijdschrift	3
DOI's	https://doi.org/10.1016/j.celrep.2014.06.048
Status	Gepubliceerd - 7 aug. 2014
Extern gepubliceerd	Ja

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10.1016/j.celrep.2014.06.048

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Deplus, R., Blanchon, L., Rajavelu, A., Boukaba, A., Defrance, M., Luciani, J., Rothé, F., Dedeurwaerder, S., Denis, H., Brinkman, A. B., Simmer, F., Müller, F., Bertin, B., Berdasco, M., Putmans, P., Calonne, E., Litchfield, D. W., De Launoit, Y., Jurkowski, T. P., ... Fuks, F. (2014). Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a. Cell reports, 8(3), 743-753. https://doi.org/10.1016/j.celrep.2014.06.048

@article{cb57a8f71c724bcbbcd0d78c5373ab24,

title = "Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a",

abstract = "DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA methylation analysis shows that CK2 primarily modulates CpG methylation of several repeats, most notably of Alu SINEs. This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. By revealing phosphorylation as a mode of regulation of de novo DNA methyltransferase function and by uncovering a mechanism for the regulation of methylation at repetitive elements, our results shed light on the origin of DNA methylation patterns.",

author = "Rachel Deplus and Lo{\"i}c Blanchon and Arumugam Rajavelu and Abdelhalim Boukaba and Matthieu Defrance and Judith Luciani and Fran{\c c}oise Roth{\'e} and Sarah Dedeurwaerder and H{\'e}l{\`e}ne Denis and Brinkman, \{Arie B.\} and Femke Simmer and Fabian M{\"u}ller and Benjamin Bertin and Maria Berdasco and Pascale Putmans and Emilie Calonne and Litchfield, \{David W.\} and \{De Launoit\}, Yvan and Jurkowski, \{Tomasz P.\} and Stunnenberg, \{Hendrik G.\} and Christoph Bock and Christos Sotiriou and Fraga, \{Mario F.\} and Manel Esteller and Albert Jeltsch and Fran{\c c}ois Fuks",

note = "Publisher Copyright: {\textcopyright} 2014 The Authors.",

year = "2014",

month = aug,

day = "7",

doi = "10.1016/j.celrep.2014.06.048",

language = "English",

volume = "8",

pages = "743--753",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "3",

}

Deplus, R, Blanchon, L, Rajavelu, A, Boukaba, A, Defrance, M, Luciani, J, Rothé, F, Dedeurwaerder, S, Denis, H, Brinkman, AB, Simmer, F, Müller, F, Bertin, B, Berdasco, M, Putmans, P, Calonne, E, Litchfield, DW, De Launoit, Y, Jurkowski, TP, Stunnenberg, HG, Bock, C, Sotiriou, C, Fraga, MF, Esteller, M, Jeltsch, A & Fuks, F 2014, 'Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a', Cell reports, vol. 8, nr. 3, blz. 743-753. https://doi.org/10.1016/j.celrep.2014.06.048

TY - JOUR

T1 - Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a

AU - Deplus, Rachel

AU - Blanchon, Loïc

AU - Rajavelu, Arumugam

AU - Boukaba, Abdelhalim

AU - Defrance, Matthieu

AU - Luciani, Judith

AU - Rothé, Françoise

AU - Dedeurwaerder, Sarah

AU - Denis, Hélène

AU - Brinkman, Arie B.

AU - Simmer, Femke

AU - Müller, Fabian

AU - Bertin, Benjamin

AU - Berdasco, Maria

AU - Putmans, Pascale

AU - Calonne, Emilie

AU - Litchfield, David W.

AU - De Launoit, Yvan

AU - Jurkowski, Tomasz P.

AU - Stunnenberg, Hendrik G.

AU - Bock, Christoph

AU - Sotiriou, Christos

AU - Fraga, Mario F.

AU - Esteller, Manel

AU - Jeltsch, Albert

AU - Fuks, François

PY - 2014/8/7

Y1 - 2014/8/7

N2 - DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA methylation analysis shows that CK2 primarily modulates CpG methylation of several repeats, most notably of Alu SINEs. This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. By revealing phosphorylation as a mode of regulation of de novo DNA methyltransferase function and by uncovering a mechanism for the regulation of methylation at repetitive elements, our results shed light on the origin of DNA methylation patterns.

AB - DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA methylation analysis shows that CK2 primarily modulates CpG methylation of several repeats, most notably of Alu SINEs. This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. By revealing phosphorylation as a mode of regulation of de novo DNA methyltransferase function and by uncovering a mechanism for the regulation of methylation at repetitive elements, our results shed light on the origin of DNA methylation patterns.

UR - https://www.scopus.com/pages/publications/84919776252

U2 - 10.1016/j.celrep.2014.06.048

DO - 10.1016/j.celrep.2014.06.048

M3 - Article

C2 - 25066127

AN - SCOPUS:84919776252

SN - 2211-1247

VL - 8

SP - 743

EP - 753

JO - Cell reports

JF - Cell reports

IS - 3

ER -

Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a

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