scholarly journals Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

2015 ◽  
Vol 112 (47) ◽  
pp. E6579-E6588 ◽  
Author(s):  
Florian Atger ◽  
Cédric Gobet ◽  
Julien Marquis ◽  
Eva Martin ◽  
Jingkui Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Mouse Liver ◽  
Mitochondrial Activity ◽  
Translation Efficiency ◽  
Mrna Transcription ◽  
Mrna Accumulation ◽  
Feeding Rhythms ◽  
Rhythmic Gene ◽  
Living Organisms

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. Although 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 WT and brain and muscle Arnt-like 1 (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 gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects 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.

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

2021 ◽  
Vol 118 (3) ◽  
pp. e2015803118
Author(s):  
Benjamin D. Weger ◽  
Cédric Gobet ◽  
Fabrice P. A. David ◽  
Florian Atger ◽  
Eva Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Mrna Expression ◽  
Restricted Feeding ◽  
Wild Type ◽  
Expression Levels ◽  
Genetic Ablation ◽  
Feeding Rhythms ◽  
Rhythmic Gene ◽  
Ad Libitum

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.

scholarly journals Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice

Cell Reports ◽  
2019 ◽  
Vol 27 (3) ◽  
pp. 649-657.e5 ◽  
Author(s):  
Ben J. Greenwell ◽  
Alexandra J. Trott ◽  
Joshua R. Beytebiere ◽  
Shanny Pao ◽  
Alexander Bosley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Circadian Clock ◽  
Rhythmic Gene

scholarly journals Critical role of deadenylation in regulating poly(A) rhythms and circadian gene expression

2019 ◽  
Author(s):  
Xiangyu Yao ◽  
Shihoko Kojima ◽  
Jing Chen
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Transcriptional Control ◽  
Critical Role ◽  
Tail Length ◽  
Circadian Gene ◽  
Gene Expression Control ◽  
Rhythmic Gene ◽  
Transcriptional Controls

AbstractThe mammalian circadian clock is deeply rooted in rhythmic regulation of gene expression. Rhythmic transcriptional control mediated by the circadian transcription factors is thought to be the main driver of mammalian circadian gene expression. However, mounting evidence has demonstrated the importance of rhythmic post-transcriptional controls, and it remains unclear how the transcriptional and post-transcriptional mechanisms collectively control rhythmic gene expression. A recent study discovered rhythmicity in poly(A) tail length in mouse liver and its strong correlation with protein expression rhythms. To understand the role of rhythmic poly(A) regulation in circadian gene expression, we constructed a parsimonious model that depicts rhythmic control imposed upon basic mRNA expression and poly(A) regulation processes, including transcription, deadenylation, polyadenylation, and degradation. The model results reveal the rhythmicity in deadenylation as the strongest contributor to the rhythmicity in poly(A) tail length and the rhythmicity in the abundance of the mRNA subpopulation with long poly(A) tails (a rough proxy for mRNA translatability). In line with this finding, the model further shows that the experimentally observed distinct peak phases in the expression of deadenylases, regardless of other rhythmic controls, can robustly group the rhythmic mRNAs by their peak phases in poly(A) tail length and in abundance of the subpopulation with long poly(A) tails. This provides a potential mechanism to synchronize the phases of target gene expression regulated by the same deadenylases. Our findings highlight the critical role of rhythmic deadenylation in regulating poly(A) rhythms and circadian gene expression.Author SummaryThe biological circadian clock regulates various bodily functions such that they anticipate and respond to the day-and-night cycle. To achieve this, the circadian clock controls rhythmic gene expression, and these genes ultimately drive the rhythmicity of downstream biological processes. As a mechanism of driving circadian gene expression, rhythmic transcriptional control has attracted the central focus. However, mounting evidence has also demonstrated the importance of rhythmic post-transcriptional controls. Here we use mathematical modeling to investigate how transcriptional and post-transcriptional rhythms coordinately control rhythmic gene expression. We have particularly focused on rhythmic regulation of the length of poly(A) tail, a nearly universal feature of mRNAs that controls mRNA stability and translation. Our model reveals that the rhythmicity of deadenylation, the process that shortens the poly(A) tail, is the dominant contributor to the rhythmicity in poly(A) tail length and mRNA translatability. Particularly, the phase of deadenylation nearly overrides the other rhythmic processes in controlling the phases of poly(A) tail length and mRNA translatability. Our finding highlights the critical role of rhythmic deadenylation in circadian gene expression control.

Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice

2019 ◽  
Author(s):  
Ben Greenwell ◽  
Alexandra Trott ◽  
Joshua Beytebiere ◽  
Shanny Pao ◽  
Alexander Bosley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Circadian Clock ◽  
Rhythmic Gene

Clockmutation facilitates accumulation of cholesterol in the liver of mice fed a cholesterol and/or cholic acid diet

2008 ◽  
Vol 294 (1) ◽  
pp. E120-E130 ◽  
Author(s):  
Takashi Kudo ◽  
Mihoko Kawashima ◽  
Toru Tamagawa ◽  
Shigenobu Shibata
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Cholic Acid ◽  
Mouse Liver ◽  
Clock Genes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Mutant Mice ◽  
Wild Type ◽  
Clock Mutant

Cholesterol (CH) homeostasis in the liver is regulated by enzymes of CH synthesis such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and catabolic enzymes such as cytochrome P-450, family 7, subfamily A, and polypeptide 1 (CYP7A1). Since a circadian clock controls the gene expression of these enzymes, these genes exhibit circadian rhythm in the liver. In this study, we examined the relationship between a diet containing CH and/or cholic acid (CA) and the circadian regulation of Hmgcr, low-density lipoprotein receptor ( Ldlr), and Cyp7a1 gene expression in the mouse liver. A 4-wk CA diet lowered and eventually abolished the circadian expression of these genes. Not only clock genes such as period homolog 2 (Drosophila) ( Per2) and brain and muscle arnt-like protein-1 ( Bmal1) but also clock-controlled genes such as Hmgcr, Ldlr, and Cyp7a1 showed a reduced and arrhythmic expression pattern in the liver of Clock mutant mice. The reduced gene expression of Cyp7a1 in mice fed a diet containing CA or CH + CA was remarkable in the liver of Clock mutants compared with wild-type mice, and high liver CH accumulation was apparent in Clock mutant mice. In contrast, a CH diet without CA only elevated Cyp7a1 expression in both wild-type and Clock mutant mice. The present findings indicate that normal circadian clock function is important for the regulation of CH homeostasis in the mouse liver, especially in conjunction with a diet containing high CH and CA.

scholarly journals HISTOLOGICAL AND IMMUNOLOGICAL STUDIES ON THE PROTECTIVE EFFECT OF EUCALYPTUS CAMALDULENSIS AGAINST ROUNDUP-INDUCED HEPATOTOXICITY IN FROGS

2019 ◽  
pp. 130-136
Author(s):  
AWADALLA EA ◽  
MOHAMED AAA ◽  
ABDELSADIK A
Keyword(s):  
Gene Expression ◽  
Direct Evidence ◽  
Eucalyptus Camaldulensis ◽  
Treated Group ◽  
Negative Control ◽  
Current Data ◽  
Mitochondrial Activity ◽  
Histopathological Changes ◽  
Considerable Debate ◽  
Living Organisms

Objective: Roundup (RUP) is a prominent utilized worldwide herbicide. Possible toxicity of RUP is a considerable debate. We studied the possible mode of RUP cytotoxicity and the antitoxic effects of Eucalyptus camaldulensis (EUC) in male of Bufo regularis. Methods: We were analyzed EUC extract scavenging activity and determined the bioactive compounds. In addition, we measured the lipid peroxidation (LPO), histopathological changes, and gene expression in the liver. Frogs were divided into negative control, EUC, RUP, and combined RUP and EUC treated (RUP+EUC) groups. Data were represented as mean±SD and considered statistically significant when p<0.05. Results: Treatment of animals with RUP increased LPO and numerous pathological changes with an increased number of melanomacrophages (MMCs). In addition, RUP-treated group revealed downregulation of different genes associated with immunity and mitochondrial activity. On the other side, RUP+EUC-treated group showed restoration of the normal hepatic structure and ultrastructural integrity for a considerable extent. The current study evidenced immune system dysregulation through recombinant activating gene 1 downregulation and overexpression of CX chemokine receptor type-4 and cytochrome c oxidase subunit I. Conclusion: The current data represent a direct evidence for the toxicity of RUP that experimentally verified by the histopathological changes, elevated LPO, and imbalanced gene expression. Moreover, aggregation of MMCs pointed to the faced immunological challenges due to RUP toxicity. We are emphasizing that uncontrolled use of RUP is potentially hazardous to the living organisms and man. The application of natural antagonists such a plant extract (e.g., EUC) can reduce biological toxicity.

scholarly journals Circadian clock-dependent and -independent posttranscriptional regulation underlies temporal mRNA accumulation in mouse liver

2018 ◽  
Vol 115 (8) ◽  
pp. E1916-E1925 ◽  
Author(s):  
Jingkui Wang ◽  
Laura Symul ◽  
Jake Yeung ◽  
Cédric Gobet ◽  
Jonathan Sobel ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Posttranscriptional Regulation ◽  
Mouse Liver ◽  
Binding Proteins ◽  
Mrna Degradation ◽  
Mrna Accumulation ◽  
Intact Mouse ◽  
Mrna Binding Proteins ◽  
Mouse Tissues ◽  
Mrna Binding

The mammalian circadian clock coordinates physiology with environmental cycles through the regulation of daily oscillations of gene expression. Thousands of transcripts exhibit rhythmic accumulations across mouse tissues, as determined by the balance of their synthesis and degradation. While diurnally rhythmic transcription regulation is well studied and often thought to be the main factor generating rhythmic mRNA accumulation, the extent of rhythmic posttranscriptional regulation is debated, and the kinetic parameters (e.g., half-lives), as well as the underlying regulators (e.g., mRNA-binding proteins) are relatively unexplored. Here, we developed a quantitative model for cyclic accumulations of pre-mRNA and mRNA from total RNA-seq data, and applied it to mouse liver. This allowed us to identify that about 20% of mRNA rhythms were driven by rhythmic mRNA degradation, and another 15% of mRNAs regulated by both rhythmic transcription and mRNA degradation. The method could also estimate mRNA half-lives and processing times in intact mouse liver. We then showed that, depending on mRNA half-life, rhythmic mRNA degradation can either amplify or tune phases of mRNA rhythms. By comparing mRNA rhythms in wild-type and Bmal1−/− animals, we found that the rhythmic degradation of many transcripts did not depend on a functional BMAL1. Interestingly clock-dependent and -independent degradation rhythms peaked at distinct times of day. We further predicted mRNA-binding proteins (mRBPs) that were implicated in the posttranscriptional regulation of mRNAs, either through stabilizing or destabilizing activities. Together, our results demonstrate how posttranscriptional regulation temporally shapes rhythmic mRNA accumulation in mouse liver.

scholarly journals Diurnal RNAPII-tethered chromatin interactions are associated with rhythmic gene expression in rice

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Li Deng ◽  
Baibai Gao ◽  
Lun Zhao ◽  
Ying Zhang ◽  
Qing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Clock Genes ◽  
High Plasticity ◽  
Spatial Clusters ◽  
Mrna Accumulation ◽  
3D Genome ◽  
Chromatin Architecture ◽  
Chromatin Interactions ◽  
Rhythmic Gene

Abstract Background The daily cycling of plant physiological processes is speculated to arise from the coordinated rhythms of gene expression. However, the dynamics of diurnal 3D genome architecture and their potential functions underlying the rhythmic gene expression remain unclear. Results Here, we reveal the genome-wide rhythmic occupancy of RNA polymerase II (RNAPII), which precedes mRNA accumulation by approximately 2 h. Rhythmic RNAPII binding dynamically correlates with RNAPII-mediated chromatin architecture remodeling at the genomic level of chromatin interactions, spatial clusters, and chromatin connectivity maps, which are associated with the circadian rhythm of gene expression. Rhythmically expressed genes within the same peak phases of expression are preferentially tethered by RNAPII for coordinated transcription. RNAPII-associated chromatin spatial clusters (CSCs) show high plasticity during the circadian cycle, and rhythmically expressed genes in the morning phase and non-rhythmically expressed genes in the evening phase tend to be enriched in RNAPII-associated CSCs to orchestrate expression. Core circadian clock genes are associated with RNAPII-mediated highly connected chromatin connectivity networks in the morning in contrast to the scattered, sporadic spatial chromatin connectivity in the evening; this indicates that they are transcribed within physical proximity to each other during the AM circadian window and are located in discrete “transcriptional factory” foci in the evening, linking chromatin architecture to coordinated transcription outputs. Conclusion Our findings uncover fundamental diurnal genome folding principles in plants and reveal a distinct higher-order chromosome organization that is crucial for coordinating diurnal dynamics of transcriptional regulation.

scholarly journals The hepatocyte insulin receptor is required to program rhythmic gene expression and the liver clock

2021 ◽  
Author(s):  
Tiffany Fougeray ◽  
Arnaud Polizzi ◽  
Marion Régnier ◽  
Anne Fougerat ◽  
Sandrine Ellero-Simatos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Circadian Clock ◽  
Insulin Receptor ◽  
Mammalian Cells ◽  
Metabolic Diseases ◽  
Hepatic Glucose Production ◽  
Hepatic Insulin Resistance ◽  
Alcoholic Fatty Liver ◽  
Rhythmic Gene

SUMMARYIn mammalian cells, gene expression is rhythmic and sensitive to various environmental and physiological stimuli. A circadian clock system helps to anticipate and synchronize gene expression with daily stimuli including cyclic light and food intake, which control the central and peripheral clock programs, respectively. Food intake also regulates insulin secretion. How much insulin contributes to the effect of feeding on the entrainment of the clock and rhythmic gene expression remains to be investigated.An important component of insulin action is mediated by changes in insulin receptor (IR)-dependent gene expression. In the liver, insulin at high levels controls the transcription of hundreds of genes involved in glucose homeostasis to promote energy storage while repressing the expression of gluconeogenic genes. In type 2 diabetes mellitus (T2DM), selective hepatic insulin resistance impairs the inhibition of hepatic glucose production while promoting lipid synthesis. This pathogenic process promoting hyperlipidemia as well as non-alcoholic fatty liver diseases.While several lines of evidence link such metabolic diseases to defective control of circadian homeostasis, the hypothesis that IR directly synchronizes the clock has not been studied in vivo. Here, we used conditional hepatocyte-restricted gene deletion to evaluate the role of IR in the regulation and oscillation of gene expression as well as in the programming of the circadian clock in adult mouse liver.

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