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Defining the mammalian coactivation of hepatic 12-hour clock and lipid metabolism

ABSTRACT: Defining the mammalian coactivation of hepatic 12-hour clock and lipid metabolism

PROVIDER: PRJNA733045 | ENA |

REPOSITORIES: ENA

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Defining the mammalian coactivation of hepatic 12-hour clock and lipid metabolism

Project description:The 12-hour clock coordinates lipid homeostasis, energy metabolism and stress rhythms via the transcriptional regulator XBP1. However, the biochemical and physiological basis for integrated control of the 12-hour clock and diverse metabolic pathways remains unclear. Here, we show that steroid receptor coactivator SRC-3 coactivates XBP1 transcription and regulates hepatic 12-hour cistrome and gene rhythmicity. Mice lacking SRC-3 show abnormal 12-hour rhythms in hepatic transcription, metabolic functions, systemic energetics, and rate-limiting lipid metabolic processes including triglyceride, phospholipid and cardiolipin pathways. Notably, 12-hour clock coactivation is not only preserved, with its cistromic activation priming ahead of the zeitgeber cue of light, but concomitant with rhythmic remodeling in the absence of food. These findings reveal that SRC-3 integrates the mammalian 12-hour clock, energy metabolism, and membrane and lipid homeostasis, and demonstrates a role for the 12-hour clock machinery as an active transcriptional mechanism in anticipating physiological and metabolic energy needs and stresses.

2022-02-04 | ST002079 | MetabolomicsWorkbench

Defining the mammalian coactivation of hepatic 12-hour clock and lipid metabolism

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

2021-12-31 | GSE175598 | GEO

Twenty-four hour rhythms in the absence of the clock gene Bmal1

Project description:Circadian (~24 hour) clocks exist in almost all types of living organism and play a fundamental role in regulating daily physiological and behavioural processes. The transcription factor BMAL1 (ARNTL) is thought to be one of the principal drivers of the molecular clock in mammals since its deletion abolishes 24-hour activity patterning, an important physiological output of the clockwork. However, whether or not Bmal1-/- mice can nevertheless display molecular 24-hour rhythms is unknown. Here, we determined whether Bmal1 function is necessary for daily molecular oscillations in two tissues – skin fibroblasts and liver. Unexpectedly, both tissues exhibited robust 24-hour oscillations over 2-3 days in the absence of any exogenous synchronizers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. Indeed, molecular oscillations were pervasive throughout the transcriptome, proteome and phosphoproteome of Bmal1-/- mice. In particular, several proteins exhibited rhythmic phosphorylation in both Bmal1-proficient and -deficient cells, highlighting an unanticipated role for post-translational regulators in 24-hour rhythms in the absence of any known clock mechanisms.

2020-02-17 | PXD009243 | Pride

Defining the Independence of the Liver Circadian Clock

Project description:Defining the Independence of the Liver Circadian Clock

| PRJNA548674 | ENA

Polysome profiling in CIRCADIAN CLOCK ASSOCIATED 1-overexpressing (CCA1-ox) Arabidopsis thaliana over a 24-hour diurnal cycle

2015-10-15 | GSE61898 | GEO

Transcript levels in CIRCADIAN CLOCK ASSOCIATED 1-overexpressing (CCA1-ox) Arabidopsis thaliana over a 24-hour diurnal cycle

2015-10-15 | GSE61896 | GEO

Proteome analysis of Arabidopsis thaliana circadian clock mutants

Project description:The circadian clock is comprised of proteins that form negative feedback loops, which regulate the timing of global gene expression in a coordinated 24 hour cycle. As a result, the plant circadian clock is responsible for regulating numerous physiological processes central to growth and survival. To date, most plant circadian clock studies have relied on diurnal transcriptome changes to elucidate molecular connections between the circadian clock and observable phenotypes in wild-type plants. Here, we have combined high-throughput RNA-sequencing and mass spectrometry to comparatively characterize the lhycca1, prr7prr9, gi and toc1 circadian clock mutant rosette transcriptome and proteome at the end-of-day and end-of-night.

2018-01-02 | PXD004763 | Pride

Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m6A mRNA Methylation [siMettl3]

Project description:Circadian transcriptional rhythms are necessary for lipid metabolic homeostasis. Disruptions can lead to metabolic diseases. Whether epigenetic N6-methyladenosine (m6A) mRNA methylation impacts circadian regulation of lipid metabolism is unclear. Here, we show m6A mRNA methylation oscillations in murine liver depend upon a functional circadian clock. Hepatic deletion of Bmal1 increased m6A mRNA methylation, particularly of PPaRα. Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreased PPaRα m6A abundance and increased PPaRα mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. Our data suggest YTH domain family 2 (YTHDF2, a m6A binding protein) binds to PPaRα, prolonging its lifetime and mRNA expression. Reactive oxygen species accumulation increased PPaRα transcript m6A levels, revealing a possible mechanism for circadian clock disruption on m6A mRNA methylation. These data suggest m6A RNA methylation is important for circadian clock regulation of downstream genes and lipid metabolism that impacts metabolic outcome.

2018-06-21 | GSE102620 | GEO

Transcript levels in CIRCADIAN CLOCK ASSOCIATED 1-overexpressing (CCA1-ox) Arabidopsis thaliana over a 24-hour diurnal cycle

Project description:Circadian control of gene expression has been established in plants at the transcriptional level, but relatively little is known about circadian control of translation. We used polysome profiling to characterize regulation of transcription and translation over a 24-hour diurnal cycle in Arabidopsis, both in wild type and in plants with a disrupted clock due to constitutive overexpression of the CIRCADIAN CLOCK ASSOCIATED 1 gene (CCA1-ox, AGI AT2G46830). 10 day-old wild type and CCA1-ox (described in Cell. 1998 Jun 26;93(7):1207-17) Arabidopsis seedlings were harvested at 6am (Zeitgeber time ZT0), 12pm (ZT6), 6pm (ZT12), and 12am (ZT18), with 3 replicates for each time and genotype.

2015-02-01 | E-GEOD-61896 | biostudies-arrayexpress

Polysome profiling in CIRCADIAN CLOCK ASSOCIATED 1-overexpressing (CCA1-ox) Arabidopsis thaliana over a 24-hour diurnal cycle

2015-02-01 | E-GEOD-61898 | biostudies-arrayexpress

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