PUBLICATION

Integrative Analysis of Circadian Transcriptome and Metabolic Network Reveals the Role of De Novo Purine Synthesis in Circadian Control of Cell Cycle

Authors
Li, Y., Li, G., Görling, B., Luy, B., Du, J., Yan, J.
ID
ZDB-PUB-150226-2
Date
2015
Source
PLoS Computational Biology   11: e1004086 (Journal)
Registered Authors
Du, Jiu Lin, Li, Ying
Keywords
Zebrafish, Circadian rhythms, Circadian oscillators, Purine metabolism, Cell cycle and cell division, Purines, Chronobiology, Larvae
Datasets
GEO:GSE51278, GEO:GSE51277
MeSH Terms
  • Animals
  • Brain/metabolism
  • Cell Cycle/physiology*
  • Circadian Rhythm/physiology*
  • Cluster Analysis
  • Fish Proteins/genetics
  • Fish Proteins/metabolism
  • Gene Knockdown Techniques
  • IMP Dehydrogenase/genetics
  • IMP Dehydrogenase/metabolism
  • Larva/growth & development
  • Larva/metabolism
  • Metabolic Networks and Pathways/physiology*
  • Purines/metabolism*
  • Transcriptome/physiology*
  • Zebrafish
PubMed
25714999 Full text @ PLoS Comput. Biol.
Abstract
Metabolism is the major output of the circadian clock in many organisms. We developed a computational method to integrate both circadian gene expression and metabolic network. Applying this method to zebrafish circadian transcriptome, we have identified large clusters of metabolic genes containing mostly genes in purine and pyrimidine metabolism in the metabolic network showing similar circadian phases. Our metabolomics analysis found that the level of inosine 5'-monophosphate (IMP), an intermediate metabolite in de novo purine synthesis, showed significant circadian oscillation in larval zebrafish. We focused on IMP dehydrogenase (impdh), a rate-limiting enzyme in de novo purine synthesis, with three circadian oscillating gene homologs: impdh1a, impdh1b and impdh2. Functional analysis revealed that impdh2 contributes to the daily rhythm of S phase in the cell cycle while impdh1a contributes to ocular development and pigment synthesis. The three zebrafish homologs of impdh are likely regulated by different circadian transcription factors. We propose that the circadian regulation of de novo purine synthesis that supplies crucial building blocks for DNA replication is an important mechanism conferring circadian rhythmicity on the cell cycle. Our method is widely applicable to study the impact of circadian transcriptome on metabolism in complex organisms.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping