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2015 ; 58
(1
): 147-56
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Bursty gene expression in the intact mammalian liver
#MMPMID25728770
Bahar Halpern K
; Tanami S
; Landen S
; Chapal M
; Szlak L
; Hutzler A
; Nizhberg A
; Itzkovitz S
Mol Cell
2015[Apr]; 58
(1
): 147-56
PMID25728770
show ga
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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