Bidirectional enhancer RNAs regulate MYB expression via different promoters in human leukemia

MYB is a pivotal oncogenic driver in leukemia. Transcriptional regulation of MYB is complex with an alternative MYB promoter located in intron 1. We identified two bidirectional enhancer RNAs transcribed from the -34 kb enhancer of MYB. These two eRNAs both upregulate MYB transcription, and promote proliferation and migration in leukemia cells. To further elucidate how eRNAs regulate MYB expression, RNA-Seq was performed to determine changes in MYB exon usage after overexpression of eRNAs in K562 cells based on DEXSeq analysis. Transcription initiating from alternative MYB promoter produces N-terminally truncated MYB protein lacking the first 20 amino acids. to analyze the genes and pathways affected by MYB isoforms, RNA-Seq was performed after MYB or N-terminally truncated MYB was overexpressed in K562 cells.