Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers
| Autor: | Cody Ashby, Brian A Walker, Marco Trevisan-Herraz, Sharmilan Thanendrarajan, Kent Fung, Agata Cieslak, Shmuel Yaccoby, Maurizio Zangari, Aneta Mikulasova, Daniel Rico, Vahid Asnafi, Lisa J. Russell, Nefeli Karataraki, Anne E. Corcoran, Daniel Kent, Sophie Hambleton, Carolina Schinke, Gareth J. Morgan, Salvatore Spicuglia, Frits van Rhee, Chris A. Brackley |
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| Rok vydání: | 2021 |
| Předmět: |
Genetics
LMO2 Epigenomics 0303 health sciences Breakpoint Chromosomal translocation Oncogenes Biology Chromatin Translocation Genetic Histones 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis biology.protein Humans Enhancer Gene Genetics (clinical) 030304 developmental biology Immunoglobulin heavy locus |
| Zdroj: | Mikulasova, A, Kent, D, Trevisan-Herraz, M, Karataraki, N, Fung, K T M, Ashby, C, Cieslak, A, Yaccoby, S, van Rhee, F, Zangari, M, Thanendrarajan, S, Schinke, C, Morgan, G J, Asnafi, V, Spicuglia, S, Brackley, C A, Corcoran, A E, Hambleton, S, Walker, B A, Rico, D & Russell, L J 2021, ' Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers ', Genome Research, vol. 2022, 32, pp. 1343-1354 . https://doi.org/10.1101/gr.276042.121 |
| ISSN: | 1549-5469 1088-9051 |
| DOI: | 10.1101/gr.276042.121 |
| Popis: | Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with enhancers, often called enhancer hijacking. We analysed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH) and proto-oncogene CCND1 that are common in B-cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with hijacking of super-enhancers of other common oncogenes in B-cell (MAF, MYC and FGFR3/NSD2) and T-cell malignancies (LMO2, TLX3 and TAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept of epigenomic translocation, where the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers. |
| Databáze: | OpenAIRE |
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