Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms
| العنوان: | Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms |
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| المؤلفون: | Nicholas E. Phillips, Florian Atger, Frédéric Gachon, Meltem Weger, Eva Martin, Cédric Gobet, Fabrice P. A. David, Aline Charpagne, Felix Naef, Benjamin D. Weger |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, feeding–fasting cycle, Circadian clock, Biology, differential rhythmicity analysis, Transcriptome, Mice, transcriptomics, Circadian Clocks, Gene expression, circadian clock, Animals, RNA, Messenger, liver metabolism, Gene, Gene knockout, Mice, Knockout, Multidisciplinary, Systems Biology, NFIL3, ARNTL Transcription Factors, Feeding Behavior, Biological Sciences, Cell biology, Circadian Rhythm, CLOCK, Cryptochromes, DNA-Binding Proteins, Basic-Leucine Zipper Transcription Factors, Gene Expression Regulation, Liver, Knockout mouse, Metabolic Networks and Pathways, Transcription Factors |
| الوصف: | Significance The rotation of the Earth around its own axis creates daily changes in the environment for virtually all living organisms. To anticipate and adapt to those changes, mammals possess an evolutionarily conserved circadian clock that controls most aspects of physiology. Using a previously undescribed analysis tool, we studied the impact of the circadian clock and its underlying feeding rhythms on hepatic gene expression. Our analysis shows that the loss of feeding rhythms in clock-disrupted animals is an important component of their phenotype. Finally, we were able to decipher the specific role of feeding rhythms, the circadian clock, and its controlled output of PARbZip transcription factors in the regulation of liver rhythmic gene expression. The circadian clock and feeding rhythms are both important regulators of rhythmic gene expression in the liver. To further dissect the respective contributions of feeding and the clock, we analyzed differential rhythmicity of liver tissue samples across several conditions. We developed a statistical method tailored to compare rhythmic liver messenger RNA (mRNA) expression in mouse knockout models of multiple clock genes, as well as PARbZip output transcription factors (Hlf/Dbp/Tef). Mice were exposed to ad libitum or night-restricted feeding under regular light–dark cycles. During ad libitum feeding, genetic ablation of the core clock attenuated rhythmic-feeding patterns, which could be restored by the night-restricted feeding regimen. High-amplitude mRNA expression rhythms in wild-type livers were driven by the circadian clock, but rhythmic feeding also contributed to rhythmic gene expression, albeit with significantly lower amplitudes. We observed that Bmal1 and Cry1/2 knockouts differed in their residual rhythmic gene expression. Differences in mean expression levels between wild types and knockouts correlated with rhythmic gene expression in wild type. Surprisingly, in PARbZip knockout mice, the mean expression levels of PARbZip targets were more strongly impacted than their rhythms, potentially due to the rhythmic activity of the D-box–repressor NFIL3. Genes that lost rhythmicity in PARbZip knockouts were identified to be indirect targets. Our findings provide insights into the diurnal transcriptome in mouse liver as we identified the differential contributions of several core clock regulators. In addition, we gained more insights on the specific effects of the feeding–fasting cycle. |
| تدمد: | 1091-6490 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46a693470944689c0b8e7971202d12c0 https://pubmed.ncbi.nlm.nih.gov/33452134 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....46a693470944689c0b8e7971202d12c0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 |
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