RT Journal
A1 Mikulasova, Aneta
A1 Kent, Daniel
A1 Trevisan-Herraz, Marco
A1 Karataraki, Nefeli
A1 Fung, Kent T.M.
A1 Ashby, Cody
A1 Cieslak, Agata
A1 Yaccoby, Shmuel
A1 van Rhee, Frits
A1 Zangari, Maurizio
A1 Thanendrarajan, Sharmilan
A1 Schinke, Carolina
A1 Morgan, Gareth J.
A1 Asnafi, Vahid
A1 Spicuglia, Salvatore
A1 Brackley, Chris A.
A1 Corcoran, Anne E.
A1 Hambleton, Sophie
A1 Walker, Brian A.
A1 Rico, Daniel
A1 Russell, Lisa J.
T1 Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers
JF Genome Research 
JO Genome Research 
YR 2022 
FD July 01 
VO 32 
IS 7 
SP 1343 
OP 1354 
DO 10.1101/gr.276042.121 
UL http://genome.cshlp.org/content/32/7/1343.abstract 
AB Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with enhancers, often called enhancer hijacking. We analyzed 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 characterized 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, in which the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers.