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

Title
Whole-genome fingerprint of the DNA methylome during human B cell differentiation
Authors
Marta Kulis;Angelika Merkel;José I Martín-Subero;Elías Campo;Ivo G Gut;Ralf Küppers;Reiner Siebert;Hendrik G Stunnenberg;Paul Flicek;Marta Gut;Alfonso Valencia;Joseph L Wiemels;Seung-Tae Lee;Marina E Fomin;Marcus O Muench;Thierry Fest;Gersende Caron;Bruno Paiva;Diego Alignani;Felipe Prosper;Xabier Agirre;Marien Pascual;Avik Datta;Laura Clarke;David Richardson;Julie Blanc;Lidia Agueda;Daniel Rico;Vera Pancaldi;Simone Ecker;Roser Vilarrasa-Blasi;Nuria Russiñol;Martí Duran-Ferrer;Néria Verdaguer-Dot;Guillem Clot;Anna Esteve;Emanuele Raineri;Renée Beekman;Giancarlo Castellano;Ronald P Schuyler;Ana C Queirós;Simon Heath
Issue Date
2015
Journal Title
Nature Genetics
ISSN
1061-4036
Citation
Nature Genetics, Vol.47(7) : 746~756, 2015
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.
URI
http://www.nature.com/ng/journal/v47/n7/full/ng.3291.html

http://ir.ymlib.yonsei.ac.kr/handle/22282913/141342
DOI
10.1038/ng.3291
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
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