TY  - JOUR
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
Y1  - 2022/07/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1343 
EP  - 1354 
DO  - 10.1101/gr.276042.121 
VL  - 32 
IS  - 7 
UR  - http://genome.cshlp.org/content/32/7/1343.abstract 
N2  - 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. 
ER  -