Liver Circadian RNA-Seq from WT and Bmal1 muscle-specific KO (mKO) mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE171432 | GEO | 2023/04/05
REPOSITORIES: GEO
Similar Datasets
Project description:Circadian (~24 hour) clocks exist in almost all types of living organism and play a fundamental role in regulating daily physiological and behavioural processes. The transcription factor BMAL1 (ARNTL) is thought to be one of the principal drivers of the molecular clock in mammals since its deletion abolishes 24-hour activity patterning, an important physiological output of the clockwork. However, whether or not Bmal1-/- mice can nevertheless display molecular 24-hour rhythms is unknown. Here, we determined whether Bmal1 function is necessary for daily molecular oscillations in two tissues – skin fibroblasts and liver. Unexpectedly, both tissues exhibited robust 24-hour oscillations over 2-3 days in the absence of any exogenous synchronizers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. Indeed, molecular oscillations were pervasive throughout the transcriptome, proteome and phosphoproteome of Bmal1-/- mice. In particular, several proteins exhibited rhythmic phosphorylation in both Bmal1-proficient and -deficient cells, highlighting an unanticipated role for post-translational regulators in 24-hour rhythms in the absence of any known clock mechanisms.
2020-02-17 | PXD009243 | Pride
Project description:Circadian clocks exist in almost all levels of living organisms and play elementary roles in the persistence of regular physiological and behavioural processes. Canonical transcription/translation feedback loop models portray BMAL1 (ARNTL) as one of the principal drivers of circadian periodicity in mammalian systems. In this integrated multi-omics study, we demonstrate, for the first time, 24 hr circadian oscillations in the expression levels of several transcripts and proteins in dexamethasone-synchronized Bmal1-/- mouse fibroblast cells and liver tissue slices. Intriguingly, daily oscillations were also observed in phosphoproteome profiles in the absence of this core clock gene. Our findings reveal that Bmal1 knockout radically alters the expression and phosphorylation patterns of mice hepatic proteome, which possibly attributes to considerably different sets of rhythmic candidates compared to wild-type. It is, therefore, reasonable to accentuate that circadian rhythms are not obliterated in mammalian systems due to deletion of the core clock genes.
2020-02-14 | GSE111696 | GEO
Project description:Mouse livers were collected at 4 hours interval at constant darkness condition after 2 weeks synchronization to ambient light dark cycle, then conducted for the ChIP-seq (Bmal1, Ruvbl2). We found Ruvbl2 rhythmically co-occupancies with Bmal1 binding sites.
2020-05-07 | GSE130505 | GEO
Project description:The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of thousands of genes and enable biological functions to anticipate the daily environmental variations. Consistent with the wide range of biological functions under clock control, rhythmic gene expression is tissue-specific, and this even if the clockwork mechanism is identical in every cell. Here we show that BMAL1 DNA binding is largely tissue-specific, through mechanisms involving differences in chromatin accessibility between tissues as well as co-binding of tissue-specific transcription factors. Our results also indicate that the ability of BMAL1 to drive tissue-specific rhythmic transcription not only relies on the activity of BMAL1 cis-regulatory elements (CREs), but also on the activity of neighboring CREs. Characterization of the physical interactions between BMAL1 CREs and other CREs by RNA Polymerase II ChIA-PET in the mouse liver reveals that most interactions are stable over the course of the day, and suggests that BMAL1-mediated rhythmic transcription relies on its ability to regulate the transcriptional activity of other CREs. Our data therefore suggest that much of BMAL1 target gene transcription depends on BMAL1 capacity at rhythmically regulating a network of enhancers.
2018-05-08 | GSE110602 | GEO
Project description:Obesity and liver diseases are associated with the disruption of the circadian clock that orchestrates mammalian physiology to optimize nutrient metabolism and storage. We show here that the activity of the circadian clock regulator BMAL1 is perturbed during liver fibrosis in humans. To understand the impact of BMAL1 perturbation in obesity and liver diseases, we assessed the impact of a high fat diet or leptin deficiency on Bmal1 knockout mice. While Bmal1 knockout mice were prone to obesity, they were protected against insulin resistance, hepatic steatosis, inflammation, and fibrosis. In addition to direct transcriptional regulation of metabolic programs by BMAL1, we show that adaptation of the growth hormone and sex hormone pathways plays a critical role in this protection. Similar endocrine perturbations correlate with the development of liver fibrosis in humans, suggesting that endocrine perturbation associated with circadian disruption is critical for the pathogenesis of metabolic and liver diseases.
2022-01-26 | GSE190221 | GEO
Project description:Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are interdependent has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence program. In this study, we show that BMAL1 in is uniquely localized to genomic motifs associated with AP-1 in senescent cells and contributes to AP-1 transcriptional control of the senescence program.
2023-08-22 | GSE229011 | GEO
Project description:While several physiological skin parameters vary in a circadian manner, the identity of genes participating in chronobiology of skin remains unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle related genes, the former peaking during the day and the latter peaking at the night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes as keratinocyte-specific deletion of Bmal1 obliterates time of day dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. Consistent with higher cellular susceptibility to UV-induced DNA damage during S phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. As maximum numbers of keratinocytes go through S phase in the late afternoon in the human epidermis, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation such that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers. Whole skin was collected at ZT22. Where ZT number indicates the number of hours elapsed from when lights are switched on. ZT0 = lights on (6am). ZT12=lights off (6pm). Het mice designate a presence of one Bmal1 mutant allele and one wt allele. KO mice designate mice germline deleted for both copies of Bmal1 allele. Total RNA was purified from the skin of each biological littermate replicate.
2012-08-01 | E-GEOD-38624 | biostudies-arrayexpress
Project description:Circadian clocks exist in almost all levels of living organisms and play elementary roles in the persistence of regular physiological and behavioural processes. Canonical transcription/translation feedback loop models portray BMAL1 (ARNTL) as one of the principal drivers of circadian periodicity in mammalian systems. In this integrated multi-omics study, we demonstrate, for the first time, 24 hr circadian oscillations in the expression levels of several transcripts and proteins in dexamethasone-synchronized Bmal1-/- mouse fibroblast cells and liver tissue slices. Intriguingly, daily oscillations were also observed in phosphoproteome profiles in the absence of this core clock gene. Our findings reveal that Bmal1 knockout radically alters the expression and phosphorylation patterns of mice hepatic proteome, which possibly attributes to considerably different sets of rhythmic candidates compared to wild-type. It is, therefore, reasonable to accentuate that circadian rhythms are not obliterated in mammalian systems due to deletion of the core clock genes.
2020-02-14 | GSE134333 | GEO
Project description:To define regulation of tissue proteomes by Bmal1, daily feeding rhythm, and the interaction, we employed Bmal1-stopFL mice, which do not express the main transcriptional activator of the molecular clock, Bmal1, except in cre recombinase-expressing cells1,2 (Figure 1A). Bmal1-stopFL mice lacking cre (Bmal1 knockout, KO) are analogous to Bmal1-null mice and display severely impaired behavioral and molecular rhythms1-3. Hepatocyte-specific Alfp-cre and skeletal muscle-specific Hsa-cre genes were introduced to generate a single line wherein both hepatocyte and skeletal muscle Bmal1 were reconstituted (Liver+Muscle-RE), i.e., rescued (Smith, Koronowski et al. 2023). This approach had the benefit of analyzing liver and muscle from the same mice but comes with the qualification that the abundance of some proteins may be influenced by Bmal1 function in the other tissue, or by a synergistic effect of Bmal1 in both tissues, rather than through rescue of local Bmal1 function alone. Proteomic anlaysis was performed in liver and skeletal muscle.
2024-01-26 | PXD040362 | Pride
Project description:Liver metabolism in mice lacking Bmal1 in adipocytes. Comparison between WT and KO revealed no differentially expressed genes at ZT12 and ZT16, and only revealed one gene at ZT8 and ZT20. In contrast many genes were differential at ZT0 and ZT4. With ZT4 having substantially more than ZT0.
2020-06-01 | GSE115264 | GEO