A single cell view of MYC's gene regulatory and oncogenic mechanism

Authors

• S Patange
• M Girvan
• D Levens
• DR Larson

Abstract

We seek to determine how the MYC oncogenic transcription factor modulates stochastic transcription in single living cells. For the last 35 years, MYC was believed to execute a gene specific program which propelled cells away from apoptosis and towards growth, cell cycle progression, and de-differentiation— eventually resulting in oncogenic transformation. Recently, several models have emerged that question the prevailing view of MYC as a gene-specific transcription factor and instead envision its oncogenic mechanism as a global amplifier to elevate the existing gene expression program in a cell. We seek to evaluate these competing paradigms of MYC’s function and shed light on its in-vivo oncogenic behavior by using single-molecule RNA fluorescence in-situ hybridization (smFISH) and live cell imaging of MYC's effect on gene expression in single cells. To simulate MYC’s oncogenic activity we overexpressed MYC in the U2-OS human osteosarcoma cell line. This cell line contains an exogenous ß-globin reporter gene, transcription of which is visualized in live cells by fluorescently tagging the RNA with the MS2-PP7 stem loop system. Our results show that MYC overexpression doubles population transcript levels of ß-globin and increases the duration and magnitude of live transcription events. To our knowledge this is the first living, single cell evidence to suggest that MYC's mechanism of action may be to interact with core transcription machinery to extend the initiation rate and duration of gene active periods.

Scientific Focus Area: Cancer Biology

This page was last updated on Friday, March 26, 2021