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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: act3 actc1 admp ankrd2 bicd2 btbd3 cirbp ckb col2a1 col3a1 cpb1 ctrb1 ctrl dhx32 eef1a1 eef1a1o foxh1.2 g6pc2 gapdh gnao1 gpi hbe1 hhatl hspb1 klf17 klf17.2 klhl41 krt19 krt62 krt7 lima1 mep1a mep1b mixer myf5 myl1 mylpf myod1 nek2 nodal3.1 nodal3.2 nodal3.3 nodal3.4 nodal5 nodal5.3 nodal5.4 nodal5.5 nodal6 odc1 sia1 sia2 sypl2 tbxt thdl17 thdl18 tmod4 tnnc2 tpi1 ventx3.1 ventx3.2 calhm2 ace2

Article Images: [+] show captions
Aanes, 2011, Pubmed [+]

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