Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks.

Détails

Ressource 1Télécharger: e8339.full.pdf (4244.22 [Ko])
Etat: Serval
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_4F782D4332E0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks.
Périodique
Molecular Systems Biology
Auteur(s)
Mallm J.P., Iskar M., Ishaque N., Klett L.C., Kugler S.J., Muino J.M., Teif V.B., Poos A.M., Großmann S., Erdel F., Tavernari D., Koser S.D., Schumacher S., Brors B., König R., Remondini D., Vingron M., Stilgenbauer S., Lichter P., Zapatka M., Mertens D., Rippe K.
ISSN
1744-4292 (Electronic)
ISSN-L
1744-4292
Statut éditorial
Publié
Date de publication
22/05/2019
Peer-reviewed
Oui
Volume
15
Numéro
5
Pages
e8339
Langue
anglais
Résumé
In chronic lymphocytic leukemia (CLL), a diverse set of genetic mutations is embedded in a deregulated epigenetic landscape that drives cancerogenesis. To elucidate the role of aberrant chromatin features, we mapped DNA methylation, seven histone modifications, nucleosome positions, chromatin accessibility, binding of EBF1 and CTCF, as well as the transcriptome of B cells from CLL patients and healthy donors. A globally increased histone deacetylase activity was detected and half of the genome comprised transcriptionally downregulated partially DNA methylated domains demarcated by CTCF CLL samples displayed a H3K4me3 redistribution and nucleosome gain at promoters as well as changes of enhancer activity and enhancer linkage to target genes. A DNA binding motif analysis identified transcription factors that gained or lost binding in CLL at sites with aberrant chromatin features. These findings were integrated into a gene regulatory enhancer containing network enriched for B-cell receptor signaling pathway components. Our study predicts novel molecular links to targets of CLL therapies and provides a valuable resource for further studies on the epigenetic contribution to the disease.
Mots-clé
DNA methylation, bivalent promoter, enhancer, gene regulatory networks, histone modifications
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/06/2019 7:45
Dernière modification de la notice
14/06/2019 7:08
Données d'usage