[HTML][HTML] Bursty gene expression in the intact mammalian liver

KB Halpern, S Tanami, S Landen, M Chapal, L Szlak…�- Molecular cell, 2015 - cell.com
KB Halpern, S Tanami, S Landen, M Chapal, L Szlak, A Hutzler, A Nizhberg, S Itzkovitz
Molecular cell, 2015cell.com
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�…
Summary
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 short mRNA 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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