MYC and RNA Polymerase II Binding Near Transcriptional End Sites Regulate the Expression of Functionally-Related Genes

MYC oncoprotein binding at promoters and enhancers influences RNA polymerase II (RNAPII)-driven gene expression. Numerous genes also bind MYC near their transcriptional end sites (TESs). This often allows direct promoter-TES contact via looping and further regulates total and “read-through” transcription that extends beyond standard termination sites. We aimed here to better clarify the rules governing TES-associated MYC and/or RNAPII binding cross-talk in human and murine cells. Using ChIPseq and RNAseq datasets from the ENCODE portal and elsewhere, MYC and RNAPII binding profiles were found to differ around TESs and transcriptional start sites (TSSs). Variations in E box flanking sequences likely accounted for the somewhat lower affinities of MYC for TES-associated sites. Motifs for numerous other transcription factors were also observed to cluster non-randomly and in close proximity to MYC and RNAPII binding site peak summits. On average, genes with TES-proximal MYC or RNAPII sites were more highly expressed than those without, although co-binding tended to be suppressive. Both normal and neoplastic proliferative stimuli altered the MYC and RNAPII binding patterns of many genes, indicating that “category switching” was common, subject to disparate external signals and often reversible. Functionally related gene sets with high levels of read-through transcription were uniformly marked by significant amounts of TES-associated MYC and/or RNAPII binding. These findings indicate that, both independently and together, MYC and RNAPII binding near TESs dynamically impact total and read-through transcription while also coordinating the expression of many common purpose gene sets.