Whole-genome fingerprint of the DNA methylome during human B cell differentiation - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Nature Genetics Année : 2015

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

Vera Pancaldi
Daniel Rico
  • Fonction : Auteur
  • PersonId : 906256
Julie Blanc
Thierry Fest
Alfonso Valencia
  • Fonction : Auteur
  • PersonId : 842405
Marta Gut
  • Fonction : Auteur
  • PersonId : 950538
Paul Flicek
  • Fonction : Auteur
  • PersonId : 919968
Reiner Siebert
  • Fonction : Auteur
  • PersonId : 904241

Résumé

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.

Mots clés

Fichier principal
Vignette du fichier
Whole-genome fingerprint of the DNA methylome_accepted.pdf (1.79 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01163753 , version 1 (04-11-2015)

Identifiants

Citer

Marta Kulis, Angelika Merkel, Simon Heath, Ana C. Queirós, Ronald P. Schuyler, et al.. Whole-genome fingerprint of the DNA methylome during human B cell differentiation. Nature Genetics, 2015, 47 (7), pp.746-756. ⟨10.1038/ng.3291⟩. ⟨hal-01163753⟩
466 Consultations
480 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More