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Impact of circadian time, feeding-fasting rhythm and the autonomous clock on chromatin accessibility

ABSTRACT: Using an "omics"-based approach, we investigated the interaction between the autonomous liver clock and feeding-fasting rhythm. Transcriptomic analysis and subsequent quantification of exonic and intronic reads revealed that transcriptional mechanisms mediate, at least in part, the integration of feeding signals by the liver clock to drive mRNA oscillations. Therefore, we performed ATAC-seq to probe the state of chromatin accessibility genome-wide. While most open chromatin regions are unchanged across genotype, time and feeding status, transcription factor (TFs) footprints showed altered activity of certain TFs in Liver-RE AL vs NF. For example, CEBPB activity is altered in Liver-RE AL and restored in NF, an observation accompanied by restored CEBPB and BMAL1 common target gene oscillations. Finally, metabolomics analysis illustrated the partial rescue of hepatic metabolism in Liver-RE NF compared to AL (extensive carbohydrate pathway oscillations), and made clear that extra-hepatic clocks contribute significantly to metabolic oscillations in the liver, particularly for pathways involving lipids. Please see the associated reference for full results.

ORGANISM(S): Mus musculus

PROVIDER: GSE154902 | GEO | 2023/04/05

REPOSITORIES: GEO

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Impact of circadian time, feeding-fasting rhythm and the autonomous clock on the transcriptome

Project description:Using an "omics"-based approach, we investigated the interaction between the autonomous liver clock and feeding-fasting rhythm. Transcriptomic analysis and subsequent quantification of exonic and intronic reads revealed that transcriptional mechanisms mediate, at least in part, the integration of feeding signals by the liver clock to drive mRNA oscillations. Therefore, we performed ATAC-seq to probe the state of chromatin accessibility genome-wide. While most open chromatin regions are unchanged across genotype, time and feeding status, transcription factor (TFs) footprints showed altered activity of certain TFs in Liver-RE AL vs NF. For example, CEBPB activity is altered in Liver-RE AL and restored in NF, an observation accompanied by restored CEBPB and BMAL1 common target gene oscillations. Finally, metabolomics analysis illustrated the partial rescue of hepatic metabolism in Liver-RE NF compared to AL (extensive carbohydrate pathway oscillations), and made clear that extra-hepatic clocks contribute significantly to metabolic oscillations in the liver, particularly for pathways involving lipids. Please see the associated reference for full results.

2022-09-13 | GSE158600 | GEO

Integration of Feeding Behaviour by the Liver Circadian Clock Reveals Network Dependency of Metabolic Rhythms [ChIP-seq]

Project description:The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Due to lack of specialized animal models, it is unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we present a model in which the interaction between feeding and the liver clock can be isolated in vivo by reconstituting Bmal1 exclusively in hepatocytes (Liver-RE) in otherwise clock-less mice. We found that the cooperative action of BMAL1 and the transcription factor CEBPB regulates daily liver metabolic transcriptional programs. Functionally, the liver clock and feeding rhythm are sufficient to drive temporal glucose homeostasis. By contrast, liver rhythms tied to redox and lipid metabolism required communication with the skeletal muscle clock, demonstrating peripheral clock cross-talk. Our results highlight how the inner workings of the clock system rely on communicating signals to maintain daily metabolism.

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Requirement for NF-kB in maintenance of molecular and behavioral circadian rhythms in mice.

Project description:Purpose: In this study we employed unbiased, genome-wide techniques to investigate how inflammation-induced NF-kB activation by acute (LPS vs. saline) and chronic (high-fat diet vs. regular chow) environmental stimuli leads to circadian disruption. Methods: We performed ChIP-seq with antibodies directed against the p65 subunit of NF-kB, CLOCK, BMAL1, H3K27Ac and RNA Poll II in livers from mice treated with LPS or saline. ChIP-seq analysis was also performed in livers from mice that were fed high-fat diet for 4 weeks or regular chow. In addition, we performed ChIP-seq with BMAL1 in mouse embryonic fibroblast deficient in p65. Results: Induction of NF-kB reconfigures the genome-wide position of core clock transcription factors. Acute (i.e. LPS) and chronic (e.g. high-fat diet) inflammation-induced NF-kB re-localizes components of the forward limb of clock (CLOCK/BMAL1) to sites convergent with NF-kB and acetylated H3K27 and enriched in RNA POL II in liver. In addition, NF-kB activation leads to higher p65 binding specific to E-box elements within the negative limb of the clock with both acute and chronic stimuli. Conclusions: Our findings cast new light on NF-kB as a pivotal genomic control node integrating metabolic inflammation and circadian systems at both the cellular and organismal levels. In particular, NF-kB directly regulates the expression of the negative limb of the clock while at the same time the clock activator TFs CLOCK/BMAL1 co-localize with NF-kB at new sites to regulate transcription following inflammatory stimuli. In addition, our data indicate significant overlap between NF-kB activation following both acute and chronic inflammatory challenges in liver.

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Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver [RNASeq]

Project description:Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5â-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5â-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. RNA-Seq from total RNA of mouse liver during the dirunal cycle. Time-series mRNA profiles of wild type (WT) and Bmal -/- mice under ad libitum and night restriced feeding regimen were generated by deep sequencing.

2015-11-10 | E-GEOD-73552 | biostudies-arrayexpress

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver [Ribosome Profiling]

Project description:Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5’-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5’-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.

2015-11-10 | GSE73553 | GEO

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver [RNASeq]

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2015-11-10 | GSE73552 | GEO

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2013-08-30 | E-GEOD-34442 | biostudies-arrayexpress

Proteomics analysis of regulation by Bmal1 and physiological time-restricted feeding

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Effect of Insulin receptor deletion in hepatocytes on liver gene expression at different time point in mice either fed ad libitum or upon day-restricted feeding

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