Single-Cell Analysis Reveals that Noncoding RNAs Contribute to Clonal Heterogeneity by Modulating Transcription Factor Recruitment

• Main Authors: Bumgarner, Stacie L. (Contributor), Neuert, Gregor (Contributor), Voight, Benjamin F (Author), Symbor-Nagrabska, Anna (Contributor), Grisafi, Paula (Contributor), van Oudenaarden, Alexander (Author), Fink, Gerald R. (Contributor), van Oudenaarden, Alexander (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Physics (Contributor), Whitehead Institute for Biomedical Research (Contributor)
• Format: Article
• Language: English
• Published: Elsevier B.V., 2014-01-08T16:46:05Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (grant M035010)
National Institutes of Health (U.S.) (grant GM40266)
National Institutes of Health (U.S.) (grant P1OD00393636)
National Science Foundation (U.S.) (grant ECCS-0835623)
Deutsche Forschungsgemeinschaft (Forschungs Stipendium)
American Cancer Society (Professor)