期刊
MOLECULAR CELL
卷 58, 期 1, 页码 147-156出版社
CELL PRESS
DOI: 10.1016/j.molcel.2015.01.027
关键词
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资金
- Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics
- Leir Charitable Foundations
- Richard Jakubskind Laboratory of Systems Biology
- Cymerman-Jakubskind Prize
- Lord Sieff of Brimpton Memorial Fund
- Human Frontiers Science Program
- I-CORE program of the Planning and Budgeting Committee
- Israel Science Foundation
- European Research Council under the European Union [335122]
- European Research Council (ERC) [335122] Funding Source: European Research Council (ERC)
Bursts of nascent mRNA have been shown to lead to substantial cell-cell variation in unicellular organisms, facilitating diverse responses to environmental challenges. It is unknown whether similar bursts and gene-expression noise occur in mammalian tissues. To address this, we combine single molecule transcript counting with dual-color labeling and quantification of nascent mRNA to characterize promoter states, transcription rates, and transcript lifetimes in the intact mouse liver. We find that liver gene expression is highly bursty, with promoters stochastically switching between transcriptionally active and inactive states. Promoters of genes with shortm-RNA lifetimes are active longer, facilitating rapid response while reducing burst-associated noise. Moreover, polyploid hepatocytes exhibit less noise than diploid hepatocytes, suggesting a possible benefit to liver polyploidy. Thus, temporal averaging and liver polyploidy dampen the intrinsic variability associated with transcriptional bursts. Our approach can be used to study transcriptional bursting in diverse mammalian tissues.
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