Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks
© 2019 The Authors. Published under the terms of the CC BY 4.0 license..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Molecular systems biology - 15(2019), 5 vom: 22. Mai, Seite e8339 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mallm, Jan-Philipp [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.05.2020 Date Revised 11.05.2020 published: Electronic Citation Status MEDLINE |
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| doi: |
10.15252/msb.20188339 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM297365312 |
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| 245 | 1 | 0 | |a Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks |
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| 500 | |a Date Revised 11.05.2020 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 The Authors. Published under the terms of the CC BY 4.0 license. | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Iskar, Murat |e verfasserin |4 aut | |
| 700 | 1 | |a Ishaque, Naveed |e verfasserin |4 aut | |
| 700 | 1 | |a Klett, Lara C |e verfasserin |4 aut | |
| 700 | 1 | |a Kugler, Sabrina J |e verfasserin |4 aut | |
| 700 | 1 | |a Muino, Jose M |e verfasserin |4 aut | |
| 700 | 1 | |a Teif, Vladimir B |e verfasserin |4 aut | |
| 700 | 1 | |a Poos, Alexandra M |e verfasserin |4 aut | |
| 700 | 1 | |a Großmann, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Erdel, Fabian |e verfasserin |4 aut | |
| 700 | 1 | |a Tavernari, Daniele |e verfasserin |4 aut | |
| 700 | 1 | |a Koser, Sandra D |e verfasserin |4 aut | |
| 700 | 1 | |a Schumacher, Sabrina |e verfasserin |4 aut | |
| 700 | 1 | |a Brors, Benedikt |e verfasserin |4 aut | |
| 700 | 1 | |a König, Rainer |e verfasserin |4 aut | |
| 700 | 1 | |a Remondini, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Vingron, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Stilgenbauer, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Lichter, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Zapatka, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Mertens, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Rippe, Karsten |e verfasserin |4 aut | |
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