MYC Amplifies Gene Expression Through Global Changes in Transcription Factor Dynamics

Abstract

The MYC oncogene has been studied intensively 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 the role of MYC in 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 bursts 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 role that appears unique among 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.