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

doi:10.1016/j.celrep.2021.110292

MYC amplifies gene expression through global changes in transcription factor dynamics

Cell Rep. 2022 Jan 25;38(4):110292. doi: 10.1016/j.celrep.2021.110292.

Authors

Simona Patange¹, David A Ball², Yihan Wan², Tatiana S Karpova², Michelle Girvan³, David Levens⁴, Daniel R Larson⁵

Affiliations

¹ 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.
² Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
³ Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA.
⁴ Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
⁵ Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: dan.larson@nih.gov.

Abstract

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.

Keywords: MYC; single-molecule imaging; transcription.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cell Line
Gene Expression Regulation / genetics*
Genes, myc / physiology*
Humans
Mice
Transcription Factors / metabolism
Transcription, Genetic / physiology*

Substances

Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding