Brd4 and CEBPB binding profiles with or without BET inhibitor JQ1 in human leukemia OCI-AML3 cells

Brd4 is the best characterized member of the bromo- and extra-terminal (BET) domain family of proteins and has been widely studied in tumor-associated transcriptional programs. Here we show that activation of Brd4 is associated with the presence of autophagy in NPMc+ and MLL AML cells. Brd4 binds to the promoters of Atg 3, 7 and CEBPb, and expression of these genes is markedly reduced by inhibitors of Brd4, as well as by Brd4-shRNA and CEBPb depletion. Inhibitors of Brd4 also dramatically suppress the transcription of Keap1, thereby increasing the expression of anti-oxidant genes through the Nrf2 pathway. We conclude that Brd4 plays a significant role in autophagy activation through the direct transcriptional regulation of genes essential for autophagy, as well as through the Keap1-Nrf2 axis in NPMc+ and MLL-fusion AML cells. Chromatin immunoprecipitation of Brd4 and CEBPB followed by high-throughput sequencing (ChIP-seq) in human NPMc+ leukemia OCI-AML3 cells in the presence or absence of BET inhibitor JQ1.