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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 
 NATURE GENETICS, Vol.47(7) : 746-756, 2015 
Journal Title
Issue Date
B-Lymphocytes/physiology* ; Base Sequence ; Cell Differentiation ; Cells, Cultured ; CpG Islands ; DNA Methylation* ; Epigenesis, Genetic/immunology* ; Gene Expression Regulation, Leukemic ; Genome, Human ; Humans ; Leukemia, B-Cell/genetics ; Sequence Analysis, DNA
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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
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