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Effect of Bmal1 post-natal knockout on liver gene expression: time-series

ABSTRACT: Gene expression in the liver has been studied extensively in normal mice, but not in mice with circadian disruption. We use a tamoxifen-inducible Lox/Cre KO mouse strain with the most important clock gene knocked out, BMAL-1. The aim of this experiment was to study the effect of circadian disruption on gene expression in the liver by comparing conditional Bmal1 KO mice with WT mice using RNA-seq. All mice were housed under 12h:12h LD conditions with free access to food and water. Seven days after the last dose of tamoxifen, mice were kept under constant darkness for 36 h and then sacrificed. Four mice per genotype were sacrificed in darkness every 4h for 20h (6 time points). Illumina TruSeq RNA Sample Prep v2 was used for library construction and samples were sequenced on an Illumina HiSeq 2000. RNA-seq data were aligned by STAR, and data were normalized with a resampling strategy (https://github.com/itmat/Normalization).

ORGANISM(S): Mus musculus

PROVIDER: GSE70497 | GEO | 2016/02/02

SECONDARY ACCESSION(S): PRJNA288820

REPOSITORIES: GEO

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Effect of Bmal1 pre-natal knockout on liver gene expression: time-series

Project description:We use a conventional (pre-natal) Bmal1 KO (cKO) mouse strain to investigate the effect of circadian disruption on gene expression in the liver by comparing cKO mice with wild type (WT) mice using RNA-Seq. All mice were housed under 12h:12h LD conditions with free access to food and water. Three mice per genotype were sacrificed every 4 h for 20 h (6 time points). Illumina TruSeq Stranded mRNA Sample Prep Kit Set A was used for library construction and samples were sequenced on an Illumina HiSeq 2500. RNA-seq data were aligned by STAR, and data were normalized with a resampling strategy (https://github.com/itmat/Normalization).

2016-02-02 | GSE70499 | GEO

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Microarray analysis of mouse cerebral cortex from brain-specific Bmal1 knockout and Per1;Per2 double mutant mice at 2 timepoints

Project description:The aim of this study was to examine the effect of genetic disruption of the circadian clock on gene expression in the cortex across timepoints. Circadian clock protein regulate many critical aspects of cellular function, and Bmal1 knockout mice develop severe neuroinflammation, suggesting a role for circadian clock gene in brain homeostatic function. We compared brain-specific Bmal1 KO mice (Nestin-Cre;Bmal1(flox/flox) with Per1/2 double mutant mice, in order to assess the effects of deletion of the positive and negative limbs of the core clock. 11mo Cre-, NestinCre+/-;Bmal1(fx/fx), or Per1brdm,Per2brdm mice were entrained to 12h light:dark conditions with lights on at 6am for one month, then placed in constant darkness for 24 hours, after which mice were harvested at 6am (CT6) or 6pm (CT18), still in the dark. Mice were anesthetized in the dark, then perfused briefly with PBS+heparin. The brain was then quickly dissected on a cold surface, and the cerebral cortex flash frozen in liquid nitrogen. Cortex samples were mechanically dissociated with a Qiashredder device, then extracted with chloroform and diluted in 70% ethanol. RNA was extracted using Qiagen RNEasy kit according to manufacturers specifications. cDNAs were chemically labeled with Kreatech ULS RNA labeling kit (Kreatech Diagnostics) and Cy5-labeled cDNAs were hybridized to Agilent Mouse v2 4x44K microarrays (G4846A-026655).

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Project description:Mice were fed a normal chow diet or a tryptophan depleted diet for two weeks under normal 12-hr light/dark cycles (LD) or in constant darkness (DD). Mice were sacrificed every 4th hour over the 24-hr circadian cycle. The liver was harvested and RNA was isolated using a standard TRIZOL protocol. The data suggest that dietary tryptophan is an important component of the diet regulating circadian homeostsis.

2023-05-30 | GSE190145 | GEO

Dietary tryptophan and circadian rhythms

Project description:Mice were fed a normal chow diet or a tryptophan depleted diet for two weeks under normal 12-hr light/dark cycles (LD) or in constant darkness (DD). Mice were sacrificed every 4th hour over the 24-hr circadian cycle. The suprachiasmatic nucleus (SCN) was harvested and RNA was isolated using a standard TRIZOL protocol. The data suggest that dietary tryptophan is an important component of the diet regulating circadian homeostsis.

2023-05-30 | GSE186242 | GEO

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

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

The effects of temporally restricted feeding on hepatic gene expression of Cry1, Cry2 double KO mice

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2009-11-23 | E-GEOD-13062 | biostudies-arrayexpress

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

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

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

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

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