Whole-genome fingerprint of the DNA methylome during human B cell differentiation

Marta Kulis; Angelika Merkel; Simon Heath; Ana C. Queirós; Ronald P. Schuyler; Giancarlo Castellano; Renée Beekman; Emanuele Raineri; Anna Esteve; Guillem Clot; Néria Verdaguer-Dot; Martí Duran-Ferrer; Nuria Russiñol; Roser Vilarrasa-Blasi; Simone Ecker; Vera Pancaldi; Daniel Rico; Lidia Agueda; Julie Blanc; David Richardson; Laura Clarke; Avik Datta; Marien Pascual; Xabier Agirre; Felipe Prosper; Diego Alignani; Bruno Paiva; Gersende Caron; Thierry Fest; Marcus O. Muench; Marina E. Fomin; Seung Tae Lee; Joseph L. Wiemels; Alfonso Valencia; Marta Gut; Paul Flicek; Hendrik G. Stunnenberg; Reiner Siebert; Ralf Küppers; Ivo G. Gut; Elías Campo; José I. Martín-Subero

doi:10.1038/ng.3291

Whole-genome fingerprint of the DNA methylome during human B cell differentiation

Marta Kulis, Angelika Merkel, Simon Heath, Ana C. Queirós, Ronald P. Schuyler, Giancarlo Castellano, Renée Beekman, Emanuele Raineri, Anna Esteve, Guillem Clot, Néria Verdaguer-Dot, Martí Duran-Ferrer, Nuria Russiñol, Roser Vilarrasa-Blasi, Simone Ecker, Vera Pancaldi, Daniel Rico, Lidia Agueda, Julie Blanc, David RichardsonLaura Clarke, Avik Datta, Marien Pascual, Xabier Agirre, Felipe Prosper, Diego Alignani, Bruno Paiva, Gersende Caron, Thierry Fest, Marcus O. Muench, Marina E. Fomin, Seung Tae Lee, Joseph L. Wiemels, Alfonso Valencia, Marta Gut, Paul Flicek, Hendrik G. Stunnenberg, Reiner Siebert, Ralf Küppers, Ivo G. Gut, Elías Campo, José I. Martín-Subero

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

249 Citaten (Scopus)

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We analyzed the DNA methylome of ten subpopulations spanning the entire B cell differentiation program by whole-genome bisulfite sequencing and high-density microarrays. We observed that non-CpG methylation disappeared upon B cell commitment, whereas CpG methylation changed extensively during B cell maturation, showing an accumulative pattern and affecting around 30% of all measured CpG sites. Early differentiation stages mainly displayed enhancer demethylation, which was associated with upregulation of key B cell transcription factors and affected multiple genes involved in B cell biology. Late differentiation stages, in contrast, showed extensive demethylation of heterochromatin and methylation gain at Polycomb-repressed areas, and genes with apparent functional impact in B cells were not affected. This signature, which has previously been linked to aging and cancer, was particularly widespread in mature cells with an extended lifespan. Comparing B cell neoplasms with their normal counterparts, we determined that they frequently acquire methylation changes in regions already undergoing dynamic methylation during normal B cell differentiation.

Originele taal-2	Engels
Pagina's (van-tot)	746-756
Aantal pagina's	11
Tijdschrift	Nature Genetics
Volume	47
Nummer van het tijdschrift	7
DOI's	https://doi.org/10.1038/ng.3291
Status	Gepubliceerd - 26 jun. 2015
Extern gepubliceerd	Ja

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10.1038/ng.3291

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Kulis, M., Merkel, A., Heath, S., Queirós, A. C., Schuyler, R. P., Castellano, G., Beekman, R., Raineri, E., Esteve, A., Clot, G., Verdaguer-Dot, N., Duran-Ferrer, M., Russiñol, N., Vilarrasa-Blasi, R., Ecker, S., Pancaldi, V., Rico, D., Agueda, L., Blanc, J., ... Martín-Subero, J. I. (2015). Whole-genome fingerprint of the DNA methylome during human B cell differentiation. Nature Genetics, 47(7), 746-756. https://doi.org/10.1038/ng.3291

@article{ceda371e68864f2ca7b82fd7423b8810,

title = "Whole-genome fingerprint of the DNA methylome during human B cell differentiation",

abstract = "We analyzed the DNA methylome of ten subpopulations spanning the entire B cell differentiation program by whole-genome bisulfite sequencing and high-density microarrays. We observed that non-CpG methylation disappeared upon B cell commitment, whereas CpG methylation changed extensively during B cell maturation, showing an accumulative pattern and affecting around 30% of all measured CpG sites. Early differentiation stages mainly displayed enhancer demethylation, which was associated with upregulation of key B cell transcription factors and affected multiple genes involved in B cell biology. Late differentiation stages, in contrast, showed extensive demethylation of heterochromatin and methylation gain at Polycomb-repressed areas, and genes with apparent functional impact in B cells were not affected. This signature, which has previously been linked to aging and cancer, was particularly widespread in mature cells with an extended lifespan. Comparing B cell neoplasms with their normal counterparts, we determined that they frequently acquire methylation changes in regions already undergoing dynamic methylation during normal B cell differentiation.",

author = "Marta Kulis and Angelika Merkel and Simon Heath and Queir{\'o}s, {Ana C.} and Schuyler, {Ronald P.} and Giancarlo Castellano and Ren{\'e}e Beekman and Emanuele Raineri and Anna Esteve and Guillem Clot and N{\'e}ria Verdaguer-Dot and Mart{\'i} Duran-Ferrer and Nuria Russi{\~n}ol and Roser Vilarrasa-Blasi and Simone Ecker and Vera Pancaldi and Daniel Rico and Lidia Agueda and Julie Blanc and David Richardson and Laura Clarke and Avik Datta and Marien Pascual and Xabier Agirre and Felipe Prosper and Diego Alignani and Bruno Paiva and Gersende Caron and Thierry Fest and Muench, {Marcus O.} and Fomin, {Marina E.} and Lee, {Seung Tae} and Wiemels, {Joseph L.} and Alfonso Valencia and Marta Gut and Paul Flicek and Stunnenberg, {Hendrik G.} and Reiner Siebert and Ralf K{\"u}ppers and Gut, {Ivo G.} and El{\'i}as Campo and Mart{\'i}n-Subero, {Jos{\'e} I.}",

year = "2015",

month = jun,

day = "26",

doi = "10.1038/ng.3291",

language = "English",

volume = "47",

pages = "746--756",

journal = "Nature Genetics",

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Kulis, M, Merkel, A, Heath, S, Queirós, AC, Schuyler, RP, Castellano, G, Beekman, R, Raineri, E, Esteve, A, Clot, G, Verdaguer-Dot, N, Duran-Ferrer, M, Russiñol, N, Vilarrasa-Blasi, R, Ecker, S, Pancaldi, V, Rico, D, Agueda, L, Blanc, J, Richardson, D, Clarke, L, Datta, A, Pascual, M, Agirre, X, Prosper, F, Alignani, D, Paiva, B, Caron, G, Fest, T, Muench, MO, Fomin, ME, Lee, ST, Wiemels, JL, Valencia, A, Gut, M, Flicek, P, Stunnenberg, HG, Siebert, R, Küppers, R, Gut, IG, Campo, E & Martín-Subero, JI 2015, 'Whole-genome fingerprint of the DNA methylome during human B cell differentiation', Nature Genetics, vol. 47, nr. 7, blz. 746-756. https://doi.org/10.1038/ng.3291

TY - JOUR

T1 - Whole-genome fingerprint of the DNA methylome during human B cell differentiation

AU - Kulis, Marta

AU - Merkel, Angelika

AU - Heath, Simon

AU - Queirós, Ana C.

AU - Schuyler, Ronald P.

AU - Castellano, Giancarlo

AU - Beekman, Renée

AU - Raineri, Emanuele

AU - Esteve, Anna

AU - Clot, Guillem

AU - Verdaguer-Dot, Néria

AU - Duran-Ferrer, Martí

AU - Russiñol, Nuria

AU - Vilarrasa-Blasi, Roser

AU - Ecker, Simone

AU - Pancaldi, Vera

AU - Rico, Daniel

AU - Agueda, Lidia

AU - Blanc, Julie

AU - Richardson, David

AU - Clarke, Laura

AU - Datta, Avik

AU - Pascual, Marien

AU - Agirre, Xabier

AU - Prosper, Felipe

AU - Alignani, Diego

AU - Paiva, Bruno

AU - Caron, Gersende

AU - Fest, Thierry

AU - Muench, Marcus O.

AU - Fomin, Marina E.

AU - Lee, Seung Tae

AU - Wiemels, Joseph L.

AU - Valencia, Alfonso

AU - Gut, Marta

AU - Flicek, Paul

AU - Stunnenberg, Hendrik G.

AU - Siebert, Reiner

AU - Küppers, Ralf

AU - Gut, Ivo G.

AU - Campo, Elías

AU - Martín-Subero, José I.

PY - 2015/6/26

Y1 - 2015/6/26

N2 - We analyzed the DNA methylome of ten subpopulations spanning the entire B cell differentiation program by whole-genome bisulfite sequencing and high-density microarrays. We observed that non-CpG methylation disappeared upon B cell commitment, whereas CpG methylation changed extensively during B cell maturation, showing an accumulative pattern and affecting around 30% of all measured CpG sites. Early differentiation stages mainly displayed enhancer demethylation, which was associated with upregulation of key B cell transcription factors and affected multiple genes involved in B cell biology. Late differentiation stages, in contrast, showed extensive demethylation of heterochromatin and methylation gain at Polycomb-repressed areas, and genes with apparent functional impact in B cells were not affected. This signature, which has previously been linked to aging and cancer, was particularly widespread in mature cells with an extended lifespan. Comparing B cell neoplasms with their normal counterparts, we determined that they frequently acquire methylation changes in regions already undergoing dynamic methylation during normal B cell differentiation.

AB - We analyzed the DNA methylome of ten subpopulations spanning the entire B cell differentiation program by whole-genome bisulfite sequencing and high-density microarrays. We observed that non-CpG methylation disappeared upon B cell commitment, whereas CpG methylation changed extensively during B cell maturation, showing an accumulative pattern and affecting around 30% of all measured CpG sites. Early differentiation stages mainly displayed enhancer demethylation, which was associated with upregulation of key B cell transcription factors and affected multiple genes involved in B cell biology. Late differentiation stages, in contrast, showed extensive demethylation of heterochromatin and methylation gain at Polycomb-repressed areas, and genes with apparent functional impact in B cells were not affected. This signature, which has previously been linked to aging and cancer, was particularly widespread in mature cells with an extended lifespan. Comparing B cell neoplasms with their normal counterparts, we determined that they frequently acquire methylation changes in regions already undergoing dynamic methylation during normal B cell differentiation.

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U2 - 10.1038/ng.3291

DO - 10.1038/ng.3291

M3 - Article

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SN - 1061-4036

VL - 47

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EP - 756

JO - Nature Genetics

JF - Nature Genetics

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ER -

Whole-genome fingerprint of the DNA methylome during human B cell differentiation

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