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Cell Rep. January 26, 2016; 14 (3): 632-47.

Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development.

Owens ND , Blitz IL , Lane MA , Patrushev I , Overton JD , Gilchrist MJ , Cho KW , Khokha MK .

Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where rapid changes in gene expression dictate cell fate decisions. By ultra-high-frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by eight orders of magnitude. Ordering genes by expression dynamics, we find that "temporal synexpression" predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology.

PubMed ID: 26774488
PMC ID: PMC4731879
Article link: Cell Rep.
Grant support: R01 GM099149 NIGMS NIH HHS , P40 OD010997 NIH HHS , R01 HD073179 NICHD NIH HHS , 5R01GM099149 NIGMS NIH HHSMedical Research Council , Cancer Research UK

Genes referenced: admp bicd2 cirbp ckb dhx32 eef1a1 eef1a1o foxh1.2 gapdh gnao1 klf17 klf17.2 krt5.5 krt5.7 lima1 mixer nek2 nodal3.1 nodal3.2 nodal3.3 nodal3.4 nodal5 nodal5.3 nodal5.4 nodal5.5 nodal6 odc1 sia1 sia2 ventx3.1 ventx3.2

Aanes, 2011, Pubmed[+]

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