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DOI10.1073/PNAS.2015803118
Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms
Weger B.D.; Gobet C.; David F.P.A.; Atger F.; Martin E.; Phillips N.E.; Charpagne A.; Weger M.; Naef F.; Gachon F.
发表日期2021
ISSN00278424
卷号118期号:3
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Circadian clock; Differential rhythmicity analysis; Feeding-fasting cycle; Liver metabolism; Transcriptomics
语种英语
scopus关键词caspase 6; cholesterol 7alpha monooxygenase; circadian rhythm signaling protein; constitutive androstane receptor; cryptochrome 1; cryptochrome 2; cyclic AMP responsive element binding protein; cyclic AMP responsive element binding protein binding protein; farnesoid X receptor; glucocorticoid; glutaredoxin; messenger RNA; nuclear receptor NR1D1; PER1 protein; PER2 protein; peroxisome proliferator activated receptor alpha; phthalic acid dibutyl ester; pregnane X receptor; retinoid related orphan receptor alpha; retinoid related orphan receptor gamma; TEPA; transcription factor ARNTL; transcription factor CLOCK; transcriptome; Agpat1 gene; animal cell; animal experiment; animal model; animal tissue; Article; binding site; biotransformation; Bmal1 gene; Casp6 gene; cell metabolism; Cirbp gene; circadian rhythm; CLOCK gene; controlled study; Cpt1a gene; Cry1 gene; Cry2 gene; Cyp7a1 gene; Dbp gene; DNA responsive element; down regulation; E box element; fasting; feeding behavior; gene; gene deletion; gene expression profiling; gene expression regulation; gene function; gene repression; gene structure; genetic algorithm; genetic analysis; genetic transcription; genotype; Hlf gene; Hsp90ab1 gene; insulin signaling; knockout mouse; liver; liver metabolism; liver size; Loxl4 gene; Lpin2 gene; male; mitochondrial biogenesis; mouse; mRNA expression level; negative feedback; Nfil3 gene; nonhuman; Npas2 gene; Nr0b2 gene; NR1D1 gene; NR1D2 gene; NR1H4 gene; NR1I2 gene; NR1I3 gene; PER1 gene; Per2 gene; Period gene; Pnpla2 gene; positive feedback; Ppar alpha gene; priority journal; RNA sequencing; RNA translation; ROR alpha gene; ROR gamma gene; Rrp12 gene; Tef gene; time series analysis; transcription regulation; transcriptome sequencing; transcriptomics; Usp2 gene; wild type mouse; xenobiotic metabolism
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/181007
作者单位Société des Produits Nestlé, Nestlé Research, Lausanne, CH-1015, Switzerland; Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, CH-1015, Switzerland; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia; Gene Expression Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, CH-1015, Switzerland; BioInformatics Competence Center, Ecole Polytechnique Fédérale de Lausanne, Lausanne, CH-1015, Switzerland; Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, CH-1015, Switzerland
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Weger B.D.,Gobet C.,David F.P.A.,et al. Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms[J],2021,118(3).
APA Weger B.D..,Gobet C..,David F.P.A..,Atger F..,Martin E..,...&Gachon F..(2021).Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA Weger B.D.,et al."Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).
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