De Novo Purine Synthesis Mediates Circadian Control of Cell Cycle in Zebrafish (array)

ABSTRACT: Cell cycle and metabolism are two major outputs controlled by circadian rhythm in many organisms. Here we show that the three processes were linked through inosine 5'-phosphate dehydrogenase (impdh), a rate-limiting enzyme in de novo purine synthesis. We using adult zebrafish as a model system,we applied a genome-wide transcriptome approach that allowed us to investigate circadian gene expression. The whole-genome transcriptome profiles of adult brain in time-series were assayed on Agilent zebrafish microarrays. We used a similar statistical method to identify zebrafish circadian genes (ZCOG) as our previous study in larval zebrafish. Three isoforms of impdh show strong circadian oscillations in different tissues of zebrafish. impdh1a contributes to the ocular development and pigment synthesis, impdh2 promotes and impdh1b delays the development. By limiting the GTP required by DNA synthesis, impdh2 contributes to the daily rhythm of S phase in cell cycle. Multiple enzymes in the de novo purine synthesis pathway show the same circadian oscillations with peaks similar to impdh2. The circadian expression of this pathway is conserved in mouse liver. In summary, we show that the circadian regulation of de novo purine synthesis that supplies crucial building blocks for DNA replication is critical for gating cell cycle in circadian rhythm. Adult zebrafish were sacrificed and dissected at 4h intervals starting at CT0 in both LD and DD conditions for 12 time points. Total RNA of individual zebrafish brain was extracted using Trizol (Invitrogen, Carlsbad, CA) according to the manufacturerM-bM-^@M-^Ys instruction. Microarrays were manufactured by Agilent Technologies (Agilent Technologies, Palo Alto, CA), containing 43,603 probes for zebrafish whole-genome transcriptional profiling.

ORGANISM(S): Danio rerio

SUBMITTER: Guang Li 

PROVIDER: E-GEOD-51277 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress