RT Journal Article SR Electronic T1 Epigenomic translocation of H3K4me3 broad domains following super-enhancer hijacking JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.12.938563 DO 10.1101/2020.02.12.938563 A1 Aneta Mikulasova A1 Marco Trevisan-Herraz A1 Kent Fung A1 Cody Ashby A1 Nefeli Karataraki A1 Gareth J. Morgan A1 Anne Corcoran A1 Sophie Hambleton A1 Brian A. Walker A1 Daniel Rico A1 Lisa J. Russell YR 2020 UL http://biorxiv.org/content/early/2020/02/12/2020.02.12.938563.abstract AB Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with super-enhancers, often called super-enhancer hijacking. We analysed the epigenomic consequences of rearrangements between the enhancers of the immunoglobulin heavy chain 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 this locus. We observed similar cancer-specific H3K4me3-BDs associated with super-enhancer hijacking of other common oncogenes in B-cell (MAF, MYC and FGFR3) and in T-cell malignancies (LMO2, TLX3 and TAL1). Our analysis suggests that H3K4me3-BDs are created by super-enhancers and supports the new concept of epigenomic translocation, where the relocation of H3K4me3-BDs accompanies the translocation of super-enhancers.