Mus musculus
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ABSTRACT:
PROVIDER: PRJNA258564 | ENA |
REPOSITORIES: ENA
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Project description:Regulatory logic of the coupled diurnal and feeding cycles in the mouse liver
| PRJNA258563 | ENA
Project description:Regulatory logic of the coupled diurnal and feeding cycles in the mouse liver [DNase-seq, ChIP-seq]
| PRJNA258229 | ENA
Project description:Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by this interconnectedness is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism – liver and skeletal muscle – by rescuing clock function either in each organ separately, or in both organs simultaneously, in otherwise clock-less mice. Experiments revealed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled with daily feeding rhythms maximizes systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis, and that disrupting this diurnal coordination can contribute to the metabolic disease.
2023-05-29 | GSE228389 | GEO
Project description:Background: Cellular iron homeostasis is regulated by iron regulatory proteins (IRP1 and IRP2) that sense iron levels (and other metabolic cues) and modulate mRNA translation or stability via interaction with iron regulatory elements (IREs). IRP2 is viewed as the primary regulator in liver, yet our previous datasets showing diurnal rhythms for certain IRE-containing mRNAs suggest a nuanced temporal control mechanism. The purpose of this study is to gain insights into the daily regulatory dynamics across IRE-bearing mRNAs, specific IRP involvement, and underlying systemic and cellular rhythmicity cues in mouse liver. Results: We uncover high-amplitude diurnal oscillations in the regulation of key IRE containing transcripts in liver, compatible with maximal IRP activity at the onset of the dark phase. Although IRP2 protein levels also exhibit some diurnal variations and peak at the light-dark transition, ribosome profiling in IRP2-deficient mice reveals that maximal repression of target mRNAs at this time-point still occurs. We further find that diurnal regulation of IRE-containing mRNAs can continue in the absence of a functional circadian clock as long as feeding is rhythmic. Conclusions: Our findings suggest temporally controlled redundancy in IRP activities, with IRP2 mediating regulation of IRE-containing transcripts in the light phase and redundancy, conceivably with IRP1, at dark onset. Moreover, we highlight the significance of feeding-associated signals in driving rhythmicity. Our work highlights the dynamic nature and regulatory complexity in a metabolic pathway that had previously been considered well-understood.
2024-05-01 | GSE243134 | GEO
Project description:Daily biological rhythms are orchestrated by a combination of the intrinsic circadian clock and external food/feeding-related signals which influence metabolism in health and disease. Understanding how and to which extent both circadian and fasting/feeding rhythms contribute to regulating daily physiology and metabolism is therefore an important ongoing effort. We generated a comprehensive proteomics dataset performing large scale time-series analysis of mouse liver obtained from feeding restricted mice over 2 full days with 16 time points in total, including as a first, a shorter post-feeding sampling-rate focus. Using our label-free absolute quantitative proteomics platform we obtained timelines with very few missing values (>99% data completeness) for over 4000 mouse liver proteoforms using 1D-LC-MS analysis of all time points and replicates (48 samples in total) allowing for robust statistical testing, as well as over 8000 mouse liver proteoforms using online 2D-LC-MS analysis of pooled replicates, providing additional depth of detection. Together our dataset provides an important resource recapitulating and extending current datasets. Our extra focus on post-feeding time points revealed a highly dynamic third metabolic period not previously observed with respect to more classic diurnal rhythmicity, providing an important addition to current knowledge.
2021-01-22 | PXD008944 | Pride
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
Project description:The circadian clock and rhythmic food intake are both important regulators of rhythmic gene expression in the liver. It remains, however, elusive to which extent the circadian clock network and natural feeding rhythms contribute to rhythmic gene expression. To systematically address this question, we developed an algorithm to investigate differential rhythmicity between a varying number of conditions. Mouse knockout models of different parts of the circadian clock network (Bmal1, Cry1/2, and Hlf/Dbp/Tef) exposed to controlled feeding regimens (ad libitum, night restricted feeding) were generated and analyzed for their temporal hepatic transcriptome. A genetical ablation of core loop elements altered feeding patterns that were restored by night restricted feeding. Mainly genes with a high amplitude were driven by the circadian clock but natural feeding patterns equally contributed to rhythmic gene expression with lower amplitude. We observed that Bmal1 and Cry1/2 KOs differed in rhythmic gene expression and identified differences in mean expression levels as a predictor for rhythmic gene expression. In Hlf/Dbp/Tef KO, mRNA levels of Hlf/Dbp/Tef target genes were decreased, albeit rhythmicity was overall preserved potentially due to the activity of the D-Box binding repressor NFIL3. Genes that lost rhythmicity in Hlf/Dbp/Tef KOs were identified to be no direct targets of PARbZip factors and presumably lost rhythmicity due to indirect effects. Collectively, our findings provide unprecedent insights into the diurnal transcriptome in mouse liver and defines the contribution of subloops of the circadian clock network and natural feeding cycles. The developed algorithm and a webapp to browse the outcomes of the study are publicly available to serve as a resource for the scientific community.
2020-12-03 | GSE135898 | GEO
Project description:The circadian clock and rhythmic food intake are both important regulators of rhythmic gene expression in the liver. It remains, however, elusive to which extent the circadian clock network and natural feeding rhythms contribute to rhythmic gene expression. To systematically address this question, we developed an algorithm to investigate differential rhythmicity between a varying number of conditions. Mouse knockout models of different parts of the circadian clock network (Bmal1, Cry1/2, and Hlf/Dbp/Tef) exposed to controlled feeding regimens (ad libitum, night restricted feeding) were generated and analyzed for their temporal hepatic transcriptome. A genetical ablation of core loop elements altered feeding patterns that were restored by night restricted feeding. Mainly genes with a high amplitude were driven by the circadian clock but natural feeding patterns equally contributed to rhythmic gene expression with lower amplitude. We observed that Bmal1 and Cry1/2 KOs differed in rhythmic gene expression and identified differences in mean expression levels as a predictor for rhythmic gene expression. In Hlf/Dbp/Tef KO, mRNA levels of Hlf/Dbp/Tef target genes were decreased, albeit rhythmicity was overall preserved potentially due to the activity of the D-Box binding repressor NFIL3. Genes that lost rhythmicity in Hlf/Dbp/Tef KOs were identified to be no direct targets of PARbZip factors and presumably lost rhythmicity due to indirect effects. Collectively, our findings provide unprecedent insights into the diurnal transcriptome in mouse liver and defines the contribution of subloops of the circadian clock network and natural feeding cycles. The developed algorithm and a webapp to browse the outcomes of the study are publicly available to serve as a resource for the scientific community.
2020-12-03 | GSE135875 | GEO
Project description:Cyclic regulatory systems are ubiquitous in cells and tissues. In the liver rhythms in mRNA expression are determined by the homeostatic regulation that operates on daily circumstances. In particular the specific response to nutrients, as well as systemic and peripheral circadian oscillators, contribute to the set up of the hepatic homeostasis at different phases of the day. In this series we used microarrays to detail the global program of gene expression in the mouse liver under physiological daily variations, determined by both the feeding and the circadian cycles.
2012-12-06 | GSE35789 | GEO