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

Dey, Siddharth S.; Foley, Jonathan E.; Limsirichai, Prajit; Schaffer, David V.; Arkin, Adam P.

doi:10.15252/msb.20145704

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

Journal Article · Tue May 05 00:00:00 EDT 2015 · Molecular Systems Biology

DOI:https://doi.org/10.15252/msb.20145704· OSTI ID:1213434

Dey, Siddharth S. ^[1]; Foley, Jonathan E. ^[1]; Limsirichai, Prajit ^[1]; Schaffer, David V. ^[2]; Arkin, Adam P. ^[2]

University of California, Berkeley, CA (United States)
University of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1213434

Journal Information:: Molecular Systems Biology, Journal Name: Molecular Systems Biology Journal Issue: 5 Vol. 11; ISSN 1744-4292

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
chromatin environment
gene expression noise
single-cell biology
single-molecule RNA FISH

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

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