Genome-wide studies identify genes directly regulated by PML/RARa fusion protein

Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) chromosome translocation that generates the promyelocytic leukemia/retinoic acid receptor-a (PML/RARa) fusion gene. However, the global association between PML/RARa and transcriptional co-regulators, and the rules of their association in governing the key processes during the leukemogenesis remain obscure. Here, we performed the genome-wide binding profiling of PML/RARa, HDAC1 and P300, in NB4, an APL patient-derived cell line. We found that PML/RARa targets could be classified into two classes. Moreover, we also performed ChIP-seq of H3K27ac to determine super-enhancers in NB4. We identified a novel function of PML/RARa in super-enhancer regulation during the leukemogenesis of APL. Overall design: Genome-wide binding profiling of PML/RARa, HDAC1, P300 and H3K27ac in NB4 cells using ChIP-seq, and expression profiling of NB4 cells before and after PML/RARa knockdown using RNA-seq.