Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_E4689F566897
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Weger B.D., Gobet C., David FPA, Atger F., Martin E., Phillips N.E., Charpagne A., Weger M., Naef F., Gachon F.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
19/01/2021
Peer-reviewed
Oui
Volume
118
Number
3
Pages
e2015803118
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
ARNTL Transcription Factors/deficiency, ARNTL Transcription Factors/genetics, Animals, Basic-Leucine Zipper Transcription Factors/genetics, Basic-Leucine Zipper Transcription Factors/metabolism, Circadian Clocks/genetics, Circadian Rhythm/genetics, Cryptochromes/deficiency, Cryptochromes/genetics, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Feeding Behavior/physiology, Gene Expression Regulation, Liver/metabolism, Male, Metabolic Networks and Pathways/genetics, Mice, Mice, Knockout, RNA, Messenger/genetics, RNA, Messenger/metabolism, Transcription Factors/genetics, Transcription Factors/metabolism, Transcriptome, circadian clock, differential rhythmicity analysis, feeding–fasting cycle, liver metabolism, transcriptomics
Pubmed
Web of science
Open Access
Yes
Create date
15/02/2021 11:36
Last modification date
28/11/2023 8:24
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