Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.

Published

Journal Article

Gene expression mediated by viral vectors is subject to cell-to-cell variability, which limits the accuracy of gene delivery. When coupled with single-cell measurements, however, such variability provides an efficient means to quantify signaling dynamics in mammalian cells. Here, we illustrate the utility of this approach by mapping the E2f1 response to MYC, serum stimulation, or both. Our results revealed an underappreciated mode of gene regulation: E2f1 expression first increased, then decreased as MYC input increased. This biphasic pattern was also reflected in other nodes of the network, including the miR-17-92 microRNA cluster and p19Arf. A mathematical model of the network successfully predicted modulation of the biphasic E2F response by serum and a CDK inhibitor. In addition to demonstrating how noise can be exploited to probe signaling dynamics, our results reveal how coordination of the MYC/RB/E2F pathway enables dynamic discrimination of aberrant and normal levels of growth stimulation.

Full Text

Duke Authors

Cited Authors

  • Wong, JV; Yao, G; Nevins, JR; You, L

Published Date

  • February 2011

Published In

Volume / Issue

  • 41 / 3

Start / End Page

  • 275 - 285

PubMed ID

  • 21292160

Pubmed Central ID

  • 21292160

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2011.01.014

Language

  • eng