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Title: Orthogonal control of expression mean and variance by epigenetic features at different genomic loci

Abstract

While gene expression noise has been shown to drive dramatic phenotypic variations, the molecular basis for this variability in mammalian systems is not well understood. Gene expression has been shown to be regulated by promoter architecture and the associated chromatin environment. However, the exact contribution of these two factors in regulating expression noise has not been explored. Using a dual-reporter lentiviral model system, we deconvolved the influence of the promoter sequence to systematically study the contribution of the chromatin environment at different genomic locations in regulating expression noise. By integrating a large-scale analysis to quantify mRNA levels by smFISH and protein levels by flow cytometry in single cells, we found that mean expression and noise are uncorrelated across genomic locations. Furthermore, we showed that this independence could be explained by the orthogonal control of mean expression by the transcript burst size and noise by the burst frequency. Finally, we showed that genomic locations displaying higher expression noise are associated with more repressed chromatin, thereby indicating the contribution of the chromatin environment in regulating expression noise.

Authors:
 [1];  [1];  [1];  [2];  [2]
  1. University of California, Berkeley, CA (United States)
  2. University of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1213434
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Molecular Systems Biology
Additional Journal Information:
Journal Volume: 11; Journal Issue: 5; Journal ID: ISSN 1744-4292
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; chromatin environment; gene expression noise; single-cell biology; single-molecule RNA FISH

Citation Formats

Dey, Siddharth S., Foley, Jonathan E., Limsirichai, Prajit, Schaffer, David V., and Arkin, Adam P. Orthogonal control of expression mean and variance by epigenetic features at different genomic loci. United States: N. p., 2015. Web. doi:10.15252/msb.20145704.
Dey, Siddharth S., Foley, Jonathan E., Limsirichai, Prajit, Schaffer, David V., & Arkin, Adam P. Orthogonal control of expression mean and variance by epigenetic features at different genomic loci. United States. doi:10.15252/msb.20145704.
Dey, Siddharth S., Foley, Jonathan E., Limsirichai, Prajit, Schaffer, David V., and Arkin, Adam P. Tue . "Orthogonal control of expression mean and variance by epigenetic features at different genomic loci". United States. doi:10.15252/msb.20145704. https://www.osti.gov/servlets/purl/1213434.
@article{osti_1213434,
title = {Orthogonal control of expression mean and variance by epigenetic features at different genomic loci},
author = {Dey, Siddharth S. and Foley, Jonathan E. and Limsirichai, Prajit and Schaffer, David V. and Arkin, Adam P.},
abstractNote = {While gene expression noise has been shown to drive dramatic phenotypic variations, the molecular basis for this variability in mammalian systems is not well understood. Gene expression has been shown to be regulated by promoter architecture and the associated chromatin environment. However, the exact contribution of these two factors in regulating expression noise has not been explored. Using a dual-reporter lentiviral model system, we deconvolved the influence of the promoter sequence to systematically study the contribution of the chromatin environment at different genomic locations in regulating expression noise. By integrating a large-scale analysis to quantify mRNA levels by smFISH and protein levels by flow cytometry in single cells, we found that mean expression and noise are uncorrelated across genomic locations. Furthermore, we showed that this independence could be explained by the orthogonal control of mean expression by the transcript burst size and noise by the burst frequency. Finally, we showed that genomic locations displaying higher expression noise are associated with more repressed chromatin, thereby indicating the contribution of the chromatin environment in regulating expression noise.},
doi = {10.15252/msb.20145704},
journal = {Molecular Systems Biology},
number = 5,
volume = 11,
place = {United States},
year = {2015},
month = {5}
}

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Cited by: 31 works
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