title: Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Wong
authors.forename: Guang
authors.initials: G
authors.lastname: Yao
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nevins
authors.forename: Lingchong
authors.initials: L
authors.lastname: You
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
chemical_list: D050687:E2F1 Transcription Factor; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D020727:ADP-Ribosylation Factors