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Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice

ABSTRACT: Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice

PROVIDER: PRJNA1254307 | ENA |

REPOSITORIES: ENA

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Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice.

Project description:Our study elucidates functional roles for conserved cis-elements associated with the evolution of mammalian hibernation. Genomic analyses found topologically associated domains (TADs) that disproportionately accumulated convergent genomic changes in hibernators, including the TAD for the Fat Mass & Obesity (Fto) locus. Some hibernation-linked cis-elements in this TAD form regulatory contacts with multiple neighboring genes. Knockout mice for these cis-elements exhibit Fto, Irx3, and Irx5 gene expression changes, impacting hundreds of genes downstream. Profiles of pre-torpor, torpor, and post-torpor phenotypes found distinct roles for each cis-element in metabolic control, while a high caloric diet uncovered different obesogenic effects. One cis-element promoting a lean phenotype influences foraging behaviors throughout life, affecting specific behavioral sequences. Thus, convergent evolution in hibernators pinpoints functional genetic mechanisms of mammalian metabolic control.

| S-EPMC11230392 | biostudies-literature

Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-09-02 | GSE295376 | GEO

Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice [RNA-seq]

Project description:Conserved cis-elements tied to hibernator evolution affect diverse metabolic traits in mice.

2025-09-02 | GSE295250 | GEO

Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice [CUT&Run]

Project description:Conserved cis-elements tied to hibernator evolution affect diverse metabolic traits in mice.

2025-09-02 | GSE295251 | GEO

Project description:Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice

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The function of the ZFP189 transcription factor in the nucleus accumbens facilitates cocaine-specific transcriptional and behavioral adaptations

Project description:Here, we explore the function of a drug-associated repressive transcription factor (TF), ZFP189, whose expression in the nucleus accumbens (NAc) facilitates cocaine-induced molecular and behavioral adaptations. To uncover the molecular action of ZFP189, we created synthetic ZFP189 TFs of distinct transcriptional function, including ZFP189VPR, which activates the expression of target genes and exerts opposite transcriptional control to the endogenously repressive ZFP189. By virally delivering synthetic ZFP189 TFs to the NAc of mice, we discover that the molecular control exerted by synthetic or endogenous ZFP189 solely alters behavioral response to cocaine but not morphine or palatable food. Transcriptional adaptation occurred in response to cocaine, but not morphine. We demonstrate that NAc ZFP189 function drives the cocaine self-administration behaviors, whereas NAc ZFP189VPR impedes this worsening of cocaine taking behaviors. Collectively, this research illuminates the mechanisms through which a drug-associated TF specifically coordinates the brain adaptations necessary for the increasing of cocaine self-administration behaviors.

2024-10-01 | GSE276453 | GEO

Analysis of molecular signatures in mammalian hibernation

Project description:Mammalian hibernators display phenotypes similar to physiological conditions in non-hibernating species under conditions of calorie restriction and fasting, hypoxia, hypothermia, ischemia-reperfusion, and sleep. However, whether or how similarities are also reflected on molecular and genetic levels is unclear. We identified molecular signatures of torpor and arousal in hibernation using a new custom-designed cDNA microarray for the arctic ground squirrel (Urocitellus parryii,) and compared them to molecular signatures of selected phenotypes in mouse. Our results show that differential gene expression related to metabolism during torpor is closely related to that during calorie restriction and hypoxia. PPARM-NM-1 is crucial for metabolic remodeling in hibernation. Genes related to the sleep-wake cycle and temperature response genes induced by hypothermia follow the same expression changes as in torpor-arousal cycle. Increased fatty acid metabolism might contribute to the protection against ischemia-reperfusion injury during hibernation. Further, by comparing with thousands of pharmacological signatures, we identified drugs that may induce similar expression patterns in human cell lines as during hibernation. Arctic ground squirrels sampled during winter hibernation were compared with the animals sampled during summer. Liver was hybridized on a custom 9,600 probes nylon membrane microarray platform. Four squirrels in early torpor, five in late torpor, four in early arousal, four in late arousal, and seven in summer active were studied in experiments.

2012-09-01 | E-GEOD-38700 | biostudies-arrayexpress

Analysis of molecular signatures in mammalian hibernation

Project description:Mammalian hibernators display phenotypes similar to physiological conditions in non-hibernating species under conditions of calorie restriction and fasting, hypoxia, hypothermia, ischemia-reperfusion, and sleep. However, whether or how similarities are also reflected on molecular and genetic levels is unclear. We identified molecular signatures of torpor and arousal in hibernation using a new custom-designed cDNA microarray for the arctic ground squirrel (Urocitellus parryii,) and compared them to molecular signatures of selected phenotypes in mouse. Our results show that differential gene expression related to metabolism during torpor is closely related to that during calorie restriction and hypoxia. PPARα is crucial for metabolic remodeling in hibernation. Genes related to the sleep-wake cycle and temperature response genes induced by hypothermia follow the same expression changes as in torpor-arousal cycle. Increased fatty acid metabolism might contribute to the protection against ischemia-reperfusion injury during hibernation. Further, by comparing with thousands of pharmacological signatures, we identified drugs that may induce similar expression patterns in human cell lines as during hibernation.

2012-09-01 | GSE38700 | GEO

Transcriptional profiling of grizzly bear skeletal muscle before and during hibernation

Project description:We report transcriptional changes in grizzly bear muscle during hibernation (February) as compared to before (October). We used Gastrocnemius muscle biopsies taken during Febrary (hibernation) and the October before (activity) for mRNA extraction followed by 454, paired-end and single-end Illumina sequencing. Resulting reads were later mapped to human homologs and used for further analysis.

2019-12-31 | GSE63864 | GEO

Liver transcriptomic and methylomic analyses identify transcriptional MAPK regulation in facultative hibernation of Syrian hamster [WGBS]

Project description:Hibernation consist of alternating torpor/arousal phases, during which animals cope with repetitive hypothermia and ischemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole genome bisulfite sequencing in liver of hibernating Syrian hamster (Mesocricetus auratus). Gene Ontology analysis was performed on 844 differentially expressed genes (DEGs) and confirmed the shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. We show a so far unreported suppression of MAPK and PP1 pathways. Notably, hibernating hamsters showed upregulation of MAPK inhibitors (DUSPs and SPRYs) and reduced levels of MAPK induced transcription factors. Promoter methylation was found to modulate the expression of genes targeted by these transcription factors. In conclusion, we document gene regulation between hibernation phases, which may aid the identification of pathways and targets to prevent organ damage in transplantation or ischemia-reperfusion.

2023-05-02 | GSE199815 | GEO

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