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

Li, Ying; Li, Guang; Görling, Benjamin 1,2; Luy, Burkhard ORCID iD icon 1,2; Du, Jiulin; Yan, Jun
1 Institut für Biologische Grenzflächen (IBG), Karlsruher Institut für Technologie (KIT)
2 Institut für Organische Chemie (IOC), Karlsruher Institut für Technologie (KIT)


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. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/110103341
Veröffentlicht am 17.01.2018
DOI: 10.1371/journal.pcbi.1004086
Zitationen: 27
Zitationen: 28
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2015
Sprache Englisch
Identifikator ISSN: 1553-734X, 1553-7358
KITopen-ID: 110103341
HGF-Programm 47.02.04 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IBG-4
Erschienen in PLoS Computational Biology
Verlag Public Library of Science (PLoS)
Band 11
Seiten 1-23
Nachgewiesen in Dimensions
Web of Science
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