Bursty gene expression in the intact mammalian liver.
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.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Keren
K
Bahar Halpern
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Sivan
S
Tanami
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Shanie
S
Landen
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Michal
M
Chapal
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Liran
L
Szlak
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Anat
A
Hutzler
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Anna
A
Nizhberg
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel. Electronic address: shalev.itzkovitz@weizmann.ac.il.
Shalev
S
Itzkovitz
D000818:Animals; D005786:Gene Expression Regulation; D006207:Half-Life; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D011003:Ploidies; D011401:Promoter Regions, Genetic; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D059010:Single-Cell Analysis; D014158:Transcription, Genetic
D012333:RNA, Messenger