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

Publication ,  Journal Article
Wong, JV; Yao, G; Nevins, JR; You, L
Published in: Molecular cell
February 2011

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.

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Published In

Molecular cell

DOI

EISSN

1097-4164

ISSN

1097-2765

Publication Date

February 2011

Volume

41

Issue

3

Start / End Page

275 / 285

Related Subject Headings

  • Proto-Oncogene Proteins c-myc
  • Mice
  • Genetic Vectors
  • Gene Expression Regulation
  • E2F1 Transcription Factor
  • Developmental Biology
  • Cell Line
  • Cell Cycle
  • Animals
  • Adenoviridae
 

Citation

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Wong, J. V., Yao, G., Nevins, J. R., & You, L. (2011). Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC. Molecular Cell, 41(3), 275–285. https://doi.org/10.1016/j.molcel.2011.01.014
Wong, Jeffrey V., Guang Yao, Joseph R. Nevins, and Lingchong You. “Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.Molecular Cell 41, no. 3 (February 2011): 275–85. https://doi.org/10.1016/j.molcel.2011.01.014.
Wong JV, Yao G, Nevins JR, You L. Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC. Molecular cell. 2011 Feb;41(3):275–85.
Wong, Jeffrey V., et al. “Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.Molecular Cell, vol. 41, no. 3, Feb. 2011, pp. 275–85. Epmc, doi:10.1016/j.molcel.2011.01.014.
Wong JV, Yao G, Nevins JR, You L. Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC. Molecular cell. 2011 Feb;41(3):275–285.
Journal cover image

Published In

Molecular cell

DOI

EISSN

1097-4164

ISSN

1097-2765

Publication Date

February 2011

Volume

41

Issue

3

Start / End Page

275 / 285

Related Subject Headings

  • Proto-Oncogene Proteins c-myc
  • Mice
  • Genetic Vectors
  • Gene Expression Regulation
  • E2F1 Transcription Factor
  • Developmental Biology
  • Cell Line
  • Cell Cycle
  • Animals
  • Adenoviridae