MYC amplifies gene expression through global changes in transcription factor dynamics
Simona Patange,
David A. Ball,
Yihan Wan,
Tatiana S. Karpova,
Michelle Girvan,
David Levens,
Daniel R. Larson
Affiliations
Simona Patange
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA
David A. Ball
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Yihan Wan
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Tatiana S. Karpova
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Michelle Girvan
Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA
David Levens
Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Daniel R. Larson
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Corresponding author
Summary: 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 an increase in the duration rather than in the frequency of bursts, a functional role that 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.
