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Endogenous circadian time genes expressions in the liver of mice under constant darkness
Citation:
Li, H., S. Zhang, W. Zhang, S. Chen, A. Rabearivony, Y. Shi, J. Liu, Jon Corton, AND C. Liu. Endogenous circadian time genes expressions in the liver of mice under constant darkness. BMC Genomics. BioMed Central Ltd, London, Uk, 21:224, (2020). https://doi.org/10.1186/s12864-020-6639-4
Impact/Purpose:
This computational biology study utilized Illumia HiSeq 3000 platform, Illumina Correlation Engine bioinformatic analysis, and qPCR verification to profile circadian gene expressions under 6-week constant darkness (DD) condition in mice. A part of this study on Angptl8 has been published (Nature Communications 10, 3158, 2019) and the sequencing data has been deposited, with the GEO number as GSE133342. The novelty of this work is the first to reveal that 8% of all the examined genes (2170 out of 27,450 genes) showed rhythmic expression patterns under DD condition at 6 time points (CT1, CT5, CT9, CT13, CT17 and CT21) during a 24 h diurnal cycle, and most of the oscillations occurred at CT13. The circadian clock core modulators, clock feedback genes, and clock-targeted genes exhibited typical oscillation pattern. The circadian oscillation of cytochrome P450 enzyme genes and genes participating in lipid and glucose metabolism would shed light on future studies in metabolism.
Description:
The circadian rhythms regulate physiological functions and metabolism. Circadian Time (CT) is a unit to quantify the time defined by each organism’s endogenous circadian clock, independent of light influence. To understand the gene expression changes throughout CT, C57BL/6J mice were maintained under constant darkness (DD) conditions for 6 weeks, and the liver samples were collected starting at 9:00 (CT1), and every 4 hours in a 24-h cycle (CT5, CT9, CT13, CT17 and CT21). Total RNA was extracted and subjected to RNA sequencing (Illumina HiSeq 3000) and real-time qPCR analysis. The sequencing data were filtered by setting a 3-fold cutoff compared to CT1 and subjected to Illumina Correlation Engine analysis. Our data revealed that approximately 8% of all the examined genes (2170 out of 27,450 genes) showed rhythmic expression patterns, and most of the changes occurred at CT13. Using CT13 as the time reference compared to other 5 CT points, 845 genes displayed oscillation. The circadian clock genes, including the core clock modulators (Arnt1, Npas2), clock feedback genes (Per1, Per2, Per3, Cry1), clock target genes (Rev-erbα, Dbp, Tef and Gm129) exhibited typical oscillation pattern. The oscillation of genes important for metabolism include our recently identified Angptl8, cytochrome P450 enzyme genes and genes participating in the lipid metabolism. RT-qPCR analysis confirmed the selected RNA sequencing results. In summary, this is the first study to profile CT gene expressions under the long-term DD condition. Our data indicate that endogenous circadian clock genes preserve typical oscillation patterns, which drive the diurnal variation of metabolic genes, even after 6 weeks of constant darkness. The oscillation of these endogenous genes could be predicted to have potential effects on intermediary and xenobiotic metabolism dependent on the time of the day.
URLs/Downloads:
DOI: Endogenous circadian time genes expressions in the liver of mice under constant darkness
https://pubmed.ncbi.nlm.nih.gov/32160860/