MYC Amplifies Gene Expression through Global Changes in Transcription Factor Dynamics

The MYC oncogene has been studied for decades, yet there is still intense debate over how this transcription factor controls gene expression. Here, we seek to answer these questions with an in vivo readout of discrete events of gene expression in single cells. We engineered an optogenetic variant of MYC (Pi-MYC) and combined this tool with single-molecule RNA and protein imaging techniques to investigate the role of MYC in modulating transcriptional bursting and transcription factor binding dynamics in human cells. We find that the immediate consequence of MYC overexpression is to increase the duration rather than frequency of bursts, a functional role which is different from the majority of human transcription factors. We further propose that the mechanism by which MYC exerts global effects on the active period of genes is by altering the binding dynamics of transcription factors involved in RNA Polymerase II complex assembly and productive elongation. SLAM-Seq profiles of human bronchial epithelial cell lines (HBEC3-KT) stably expressing photo-inducible MYC-mCherry (Pi-MYC) or a photo-inducible mCherry control (Pi-mCherry), cultured for 180min in the dark or under blue light. Data provided includes 2 biological replicates of each condition.