Single-Cell Analysis Reveals that Noncoding RNAs Contribute to Clonal Heterogeneity by Modulating Transcription Factor Recruitment
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Author(s)
Bumgarner, Stacie L.
Neuert, Gregor
Voight, Benjamin F.
Symbor-Nagrabska, Anna
Grisafi, Paula
van Oudenaarden, Alexander
Fink, Gerald R.
van Oudenaarden, Alexander
Date Issued
February 2012
Journal
Molecular Cell
Publisher
Elsevier B.V.
Citation
Bumgarner, Stacie L., Gregor Neuert, Benjamin F. Voight, Anna Symbor-Nagrabska, Paula Grisafi, Alexander van Oudenaarden, and Gerald R. Fink. “Single-Cell Analysis Reveals that Noncoding RNAs Contribute to Clonal Heterogeneity by Modulating Transcription Factor Recruitment.” Molecular Cell 45, no. 4 (February 2012): 470-482. © 2012 Elsevier.
Version
Final published version
Abstract
Mechanisms through which long intergenic noncoding RNAs (ncRNAs) exert regulatory effects on eukaryotic biological processes remain largely elusive. Most studies of these phenomena rely on methods that measure average behaviors in cell populations, lacking resolution to observe the effects of ncRNA transcription on gene expression in a single cell. Here, we combine quantitative single-molecule RNA FISH experiments with yeast genetics and computational modeling to gain mechanistic insights into the regulation of the Saccharomyces cerevisiae protein-coding gene FLO11 by two intergenic ncRNAs, ICR1 and PWR1. Direct detection of FLO11 mRNA and these ncRNAs in thousands of individual cells revealed alternative expression states and provides evidence that ICR1 and PWR1 contribute to FLO11's variegated transcription, resulting in Flo11-dependent phenotypic heterogeneity in clonal cell populations by modulating recruitment of key transcription factors to the FLO11 promoter.
MIT Department
Massachusetts Institute of Technology. Department of Physics
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2011.11.029
