Functional dissection of IGH regulatory regions in B-cell non-Hodgkin lymphoma
Characteristic feature of B-cell non-Hodgkin lymphoma are recurrent translocations juxtaposing an oncogene (e.g. MYC, BCL2) to the regulatory regions of immunoglobulin heavy chain (IGH) locus. Survival and proliferation of many B-cell lymphomas depends on the expression of the translocated oncogene and on signaling from B-cell receptor expressed from the other functional IGH allele. The goal of this project is to identify the functional regions in IGH regulatory elements and enhancer RNAs (eRNA) essential for B-cell lymphoma cell growth. We will use CRISPR/Cas9 to target all possible sites in IGH regulatory regions. In parallel, GRO-seq will identify eRNAs expressed from the IGH locus. Intersection of the results and functional follow-up will identify regulatory elements and eRNAs essential for growth of B-cell lymphoma. The results will provide new insights into the role of IGH regulatory regions in malignant cells and may indicate novel therapeutic targets in B-cell lymphoma.
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