Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA156457 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE34018: Integral roles for Rev-erb alpha and Rev-erb beta in the circadian clock function [Expression array] GSE34019: Integral roles for Rev-erb alpha and Rev-erb beta in the circadian clock function [ChIP_seq] Refer to individual Series
2012-03-28 | E-GEOD-34020 | biostudies-arrayexpress
Project description:The circadian clock acts at the genomic level to coordinate internal behavioral and physiologic rhythms via the CLOCK-BMAL transcriptional heterodimer. Although the nuclear receptors REV-ERB? and ? have been proposed to contribute to clock function, their precise roles and importance remain unresolved. To establish their regulatory potential we generated comparative cistromes of both Rev-erb isoforms, which revealed shared recognition at over ~50% of their total sites and extensive overlap with the master clock regulator Bmal. While Rev-erb? has been shown to directly regulate Bmal expression, the cistromic analysis reveals a more profound connection between Bmal and Rev-erb? and ? regulatory circuits than previously suspected. Genes within the intersection of the Bmal and Rev-erb cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erb?/? function by creating double-knockout mice (DKOs) profoundly disrupted circadian expression of core clock and lipid homeostatic genes. As a result, DKOs show strikingly altered circadian wheel-running behavior and deregulated lipid metabolism. These data reveal an integral role of Rev-erb?/? in clock function as well as provide a cistromic basis for the integration of circadian rhythm and metabolism. Total RNA was obtained from livers of wild-type and Liver-specific Reverb alpha/beta double knockout mice at ZT 0, 4, 8, 12, 16, and 20.
2012-03-28 | E-GEOD-34018 | biostudies-arrayexpress
Project description:The circadian clock acts at the genomic level to coordinate internal behavioral and physiologic rhythms via the CLOCK-BMAL transcriptional heterodimer. Although the nuclear receptors REV-ERBα and β have been proposed to contribute to clock function, their precise roles and importance remain unresolved. To establish their regulatory potential we generated comparative cistromes of both Rev-erb isoforms, which revealed shared recognition at over ~50% of their total sites and extensive overlap with the master clock regulator Bmal. While Rev-erbα has been shown to directly regulate Bmal expression, the cistromic analysis reveals a more profound connection between Bmal and Rev-erbα and β regulatory circuits than previously suspected. Genes within the intersection of the Bmal and Rev-erb cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erbα/β function by creating double-knockout mice (DKOs) profoundly disrupted circadian expression of core clock and lipid homeostatic genes. As a result, DKOs show strikingly altered circadian wheel-running behavior and deregulated lipid metabolism. These data reveal an integral role of Rev-erbα/β in clock function as well as provide a cistromic basis for the integration of circadian rhythm and metabolism. Identification of Reverb alpha and Reverb beta binding sites in mouse liver at ZT8
2012-03-28 | E-GEOD-34019 | biostudies-arrayexpress
Project description:Integral roles for Rev-erb alpha and Rev-erb beta in the circadian clock function [ChIP_seq]
| PRJNA156459 | ENA
Project description:The circadian clock acts at the genomic level to coordinate internal behavioral and physiologic rhythms via the CLOCK-BMAL transcriptional heterodimer. Although the nuclear receptors REV-ERBα and β have been proposed to contribute to clock function, their precise roles and importance remain unresolved. To establish their regulatory potential we generated comparative cistromes of both Rev-erb isoforms, which revealed shared recognition at over ~50% of their total sites and extensive overlap with the master clock regulator Bmal. While Rev-erbα has been shown to directly regulate Bmal expression, the cistromic analysis reveals a more profound connection between Bmal and Rev-erbα and β regulatory circuits than previously suspected. Genes within the intersection of the Bmal and Rev-erb cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erbα/β function by creating double-knockout mice (DKOs) profoundly disrupted circadian expression of core clock and lipid homeostatic genes. As a result, DKOs show strikingly altered circadian wheel-running behavior and deregulated lipid metabolism. These data reveal an integral role of Rev-erbα/β in clock function as well as provide a cistromic basis for the integration of circadian rhythm and metabolism.
2012-03-29 | GSE34018 | GEO
Project description:The circadian clock acts at the genomic level to coordinate internal behavioral and physiologic rhythms via the CLOCK-BMAL transcriptional heterodimer. Although the nuclear receptors REV-ERBα and β have been proposed to contribute to clock function, their precise roles and importance remain unresolved. To establish their regulatory potential we generated comparative cistromes of both Rev-erb isoforms, which revealed shared recognition at over ~50% of their total sites and extensive overlap with the master clock regulator Bmal. While Rev-erbα has been shown to directly regulate Bmal expression, the cistromic analysis reveals a more profound connection between Bmal and Rev-erbα and β regulatory circuits than previously suspected. Genes within the intersection of the Bmal and Rev-erb cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erbα/β function by creating double-knockout mice (DKOs) profoundly disrupted circadian expression of core clock and lipid homeostatic genes. As a result, DKOs show strikingly altered circadian wheel-running behavior and deregulated lipid metabolism. These data reveal an integral role of Rev-erbα/β in clock function as well as provide a cistromic basis for the integration of circadian rhythm and metabolism.
2012-03-29 | GSE34019 | GEO
Project description:The molecular circadian clock is a ubiquitous transcriptional-translational feedback loop that regulates CNS function, glial responses, and neurodegenerative pathology. The druggable nuclear receptors REV-ERB-ɑ (gene: Nr1d1) and REV-ERB-.Beta. (gene: Nr1d2) are components of the core circadian clock. REV-ERB proteins regulate neuroinflammatory responses, synaptic pruning, and protein aggregation, though the cell type-specific effects and relative compensatory effects of REV-ERB-ɑ AND -.Beta. in the brain are unknown. To study the CNS functions of REV-ERBs, we developed mouse lines with global or astrocyte-specific, conditional knockout of both REV-ERB-ɑ and -.Beta.. We demonstrate that inducible post-natal global deletion of REV-ERB-ɑ and -.Beta. in vivo results in robust spontaneous astrocyte activation and increases gene expression of disease-relevant pathways such as protein catabolism, complement, and oxidative stress. Furthermore, in vivo astrocyte-specific deletion of REV-ERB-ɑ/-.Beta. recapitulates the spontaneous astrocyte activation phenotype seen in global REV-ERB-ɑ/-.Beta. KO mice, as well as in mice with deletion of key core clock gene Bmal1, indicating that REV-ERBs regulate astrocyte activation in a cell-autonomous manner downstream of the core circadian clock. REV-ERB-ɑ/-.Beta. repress transcription of Stat3 in the brain, and deletion of REV-ERBs in astrocytes induces increased astrocytic STAT3 expression and downstream STAT3-mediated gene changes, a mechanistic link to the astrocyte reactivity shift. This astrocyte activation phenotype decreases alpha-synuclein pathology in an in vivo model of Parkinson’s Disease-related alpha-synucleinopathy and increases astrocytic protein uptake and degradation in vitro. This study therefore provides insight into astrocyte function and could elucidate novel regulatory mechanisms that are candidates for therapeutic manipulation through modulating REV-ERB activity.
2026-01-14 | GSE293033 | GEO
Project description:The molecular circadian clock is a ubiquitous transcriptional-translational feedback loop that regulates CNS function, glial responses, and neurodegenerative pathology. The druggable nuclear receptors REV-ERB-ɑ (gene: Nr1d1) and REV-ERB-.Beta. (gene: Nr1d2) are components of the core circadian clock. REV-ERB proteins regulate neuroinflammatory responses, synaptic pruning, and protein aggregation, though the cell type-specific effects and relative compensatory effects of REV-ERB-ɑ AND -.Beta. in the brain are unknown. To study the CNS functions of REV-ERBs, we developed mouse lines with global or astrocyte-specific, conditional knockout of both REV-ERB-ɑ and -.Beta.. We demonstrate that inducible post-natal global deletion of REV-ERB-ɑ and -.Beta. in vivo results in robust spontaneous astrocyte activation and increases gene expression of disease-relevant pathways such as protein catabolism, complement, and oxidative stress. Furthermore, in vivo astrocyte-specific deletion of REV-ERB-ɑ/-.Beta. recapitulates the spontaneous astrocyte activation phenotype seen in global REV-ERB-ɑ/-.Beta. KO mice, as well as in mice with deletion of key core clock gene Bmal1, indicating that REV-ERBs regulate astrocyte activation in a cell-autonomous manner downstream of the core circadian clock. REV-ERB-ɑ/-.Beta. repress transcription of Stat3 in the brain, and deletion of REV-ERBs in astrocytes induces increased astrocytic STAT3 expression and downstream STAT3-mediated gene changes, a mechanistic link to the astrocyte reactivity shift. This astrocyte activation phenotype decreases alpha-synuclein pathology in an in vivo model of Parkinson’s Disease-related alpha-synucleinopathy and increases astrocytic protein uptake and degradation in vitro. This study therefore provides insight into astrocyte function and could elucidate novel regulatory mechanisms that are candidates for therapeutic manipulation through modulating REV-ERB activity.
2026-01-14 | GSE293026 | GEO
Project description:Rev-erbα/β are druggable components of the molecular circadian clock. Rev-erb agonists can mitigate pressure overload-induced cardiac hypertrophy and myocardial infarction in mice, while Rev-erb antagonist increases myocardial ischemia-reperfusion tolerance ex vivo at the sleep-to-wake transitionHow cardiac Rev-erb regulates heart function has not been studied in vivo. ChIP-seq of Rev-erbα in the heart confirmed the robust diurnal rhythmicity of Rev-erbα genome binding with about 5 times more binding at ZT9 than at ZT21.
2021-12-08 | GSE153150 | GEO