Genome-wide studies identify the role of PML/RARa phase separation in PML/RARa and BRD4 chromatin occupancy

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 unclear. Here, we performed the genome-wide binding profiling of PML/RARa and BRD4 in NB4, an APL patient-derived cell line. Moreover, we also performed ChIP-seq of PML/RARa and BRD4 upon genetic or pharmacological pertubation of PML/RARa or BRD4 to determine how they target regulatory elements. Overall design: Genome-wide binding profiling of PML/RARa and BRD4 in NB4 cells with endogenous PML/RARa knock-down and replaced with empty vector or full-length PML/RARa or phase separation-imcompetent mutants (F158E or ?IDR) using ChIP-seq.