Journal
MOLECULAR CELL
Volume 58, Issue 2, Pages 339-352Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2015.03.005
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Funding
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1350601] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Mathematical Sciences [1312926] Funding Source: National Science Foundation
- Howard Hughes Medical Institute Funding Source: Medline
- NHGRI NIH HHS [R01HG007173, R01 HG007173] Funding Source: Medline
- NIH HHS [DP2 OD008514, 1DP2OD008514] Funding Source: Medline
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Individual mammalian cells exhibit large variability in cellular volume, even with the same absolute DNA content, and so must compensate for differences in DNA concentration in order to maintain constant concentration of gene expression products. Using single-molecule counting and computational image analysis, we show that transcript abundance correlates with cellular volume at the single-cell level due to increased global transcription in larger cells. Cell fusion experiments establish that increased cellular content itself can directly increase transcription. Quantitative analysis shows that this mechanism measures the ratio of cellular volume to DNA content, most likely through sequestration of a transcriptional factor to DNA. Analysis of transcriptional bursts reveals a separate mechanism for gene dosage compensation after DNA replication that enables proper transcriptional output during early and late S phase. Our results provide a framework for quantitatively understanding the relationships among DNA content, cell size, and gene expression variability in single cells.
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