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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_4F782D4332E0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks.
Journal
Molecular Systems Biology
Author(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
Publication state
Published
Issued date
22/05/2019
Peer-reviewed
Oui
Volume
15
Number
5
Pages
e8339
Language
english
Abstract
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.
Keywords
DNA methylation, bivalent promoter, enhancer, gene regulatory networks, histone modifications
Pubmed
Web of science
Open Access
Yes
Create date
13/06/2019 6:45
Last modification date
20/08/2019 14:05
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