Epigenetic regulation of FLT3 by ZNF384-fusion protein

Profiling global gene expression in large ALL cohorts, we identified unique over-expression of FLT3 in ZNF384-rearranged ALL, consistently across cases harboring different fusion partners with ZNF384. Mechanistically, we discovered an intergenic enhancer element at the FLT3 locus that is exclusively activated in ZNF384-rearranged ALL, with the enhancer-promoter looping directly mediated by the fusion protein. There was also a striking global enrichment of active enhancers within ZNF384 binding sites across the genome in ZNF384-rearranged ALL cells. Overall design: Characterize the local chromatin status of FLT3 gene locus