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Coactivator-Dependent Oscillation of Chromatin Accessibility Dictates Circadian Gene Amplitude through REV-ERB Loading

ABSTRACT: Coactivator-Dependent Oscillation of Chromatin Accessibility Dictates Circadian Gene Amplitude through REV-ERB Loading

PROVIDER: PRJNA281080 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1973440.fastq.gz	Fastqsanger.gz
	SRR1973441.fastq.gz	Fastqsanger.gz
	SRR1973481_1.fastq.gz	Fastqsanger.gz
	SRR1973481_2.fastq.gz	Fastqsanger.gz
	SRR1973442.fastq.gz	Fastqsanger.gz

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Integral roles for Rev-erb alpha and Rev-erb beta in the circadian clock function

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Integral roles for Rev-erb alpha and Rev-erb beta in the circadian clock function [Expression array]

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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.

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Project description:Based upon integrated analysis of transcriptomes and cistromes in Rev-erb alpha knock-out mice, we found that beta-Klotho (KLB) mRNA and protein are markedly induced in white adipose tissue but not in brown adipose tissue or liver of mice lacking Rev-erb alpha. In order to address the mechanism of the tissue-specific regulation of Klb transcription by Rev-erb apha, we performed global run-on followed by high-throughput sequencing (GRO-seq) to measure nascent transcription in different tissues in wildtype mice and Rev-erb alpha knock-out mice.

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