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Bmal1 and Rev-erb⍺ cistromes in skeletal muscle

ABSTRACT: We mapped the genome-wide binding profiles of BMAL1 and REV-ERB⍺ during peak protein expression of each factor (ZT4, and ZT8, respectively) by ChIP-Seq in gastrocnemius muscles from control C57BL/6J mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE108650 | GEO | 2018/07/20

REPOSITORIES: GEO

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Bmal1 and Rev-erb⍺ cistromes in skeletal muscle

Project description:Bmal1 and Rev-erb⍺ cistromes in skeletal muscle

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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

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2012-03-28 | E-GEOD-34020 | biostudies-arrayexpress

Rev-erb alpha citrome in brown adipose tissue

Project description:We have reported that cold temperature challenge results in a dramatic decrease in levels of the transcriptional repressor, Rev-erb alpha. Performing Rev-erb alpha ChIP-seq on brown adipose from wildtype animals kept at thermoneutrality or cold-challenged (and using Rev-erb alpha KO brown adipose as a control), we were able to globally determine the genomic regions undergoing Rev-erb alpha-dependent de-repression.

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Microarray of hippocampus from 5mo wt, Bmal1 KO and Nr1d1 (Rev-Erb-alpha) KO mice at a single timepoint

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The circadian clock components BMAL1 and REV-ERB? regulate flavivirus replication

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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.

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Project description:The circadian clock components BMAL1 and REV-ERB? regulate flavivirus replication

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Myocardial Rev-erb regulates metabolic diurnal rhythm in heart failure

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.

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Rev-erb(alpha) and (beta) Coordinately Protect the Circadian Clock and Normal Metabolic Function

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