Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102620 | GEO | 2018/06/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m6A mRNA Methylation [Bmal1 KO]

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.

2018-10-25 | GSE102619 | GEO

Homo sapiens

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

| PRJNA398233 | ENA

A photoregulatory mechanism of the circadian clock in plants [MeRIP-seq]

Project description:Circadian clocks are the time-keeping cellular apparatuses that are photoentrained according to the day-night photocycles on Earth 1,2. Cryptochromes (CRYs) are photoreceptors mediating photoentrainment of the circadian clock in plants and animals but how CRYs mediate light regulation of the molecular clock remains unclear 1,3. Here we show that CRYs mediate photoresponses of the circadian clock by regulating the activity of N6-methyladenosine (m6A) RNA methyltransferase and photoresponses of the epitranscriptome. In contrast to the presently known CRY complexome, the CRY2-methyltransferase complex exbibits multivalent interactions and photoresponsive condensation in response to blue light. We show that photoexcited CRY2 undergoes phosphorylation-assisted demixing to form photobodies with the properties of condensed liquid phase, which facilitates assembly of the CRY2-methyltransferase complex in the condensed liquid phase of CRY2 in vivo. The mta mutant impaired in m6A methyltransferase and the cry1cry2 mutant missing CRY photoreceptors share common defects of lengthened circadian period, reduced m6A RNA methylation, and accelerated degradation of mRNAs encoding core components of the molecular clock. These results argue for a photoentrainment mechanism by which blue light elicits liquid-liquid phase separation of the CRY2-methyltransferase complex to regulate m6A mRNA methylation, consequently suppressing mRNA degradation and period lengthening of the circadian clock

2021-07-12 | GSE152465 | GEO

A photoregulatory mechanism of the circadian clock in plants [RNA-seq]

2021-07-12 | GSE152464 | GEO

Mus musculus

Project description:Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m6A mRNA Methylation [Bmal1 KO]

| PRJNA398232 | ENA

The intestinal microbiota regulates body composition through NFIL3 and the circadian clock

Project description:The intestinal microbiota has been identified as an environmental factor that markedly impacts energy storage and body fat accumulation, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells and the amplitude of the circadian oscillation is controlled by the microbiota through type 3 innate lymphoid cells (ILC3), STAT3, and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.

2017-09-26 | GSE100339 | GEO

Circadian-clock independent ultradian rhythms in lipid metabolism in Drosophila fat body

Project description:The role of circadian clocks in regulating metabolic processes has been studied extensively. Yet, the physiological impacts of the circadian system on metabolic states across species and life stages remain to be explored. This study investigates the relationship between circadian rhythms and metabolic regulation in the fat body of Drosophila larva, an organ crucial for maintaining metabolic homeostasis, growth and developmental timing. Larval fat body is analogous to the mammalian liver and adipose tissue but lacks a canonical circadian clock. Around-the-clock RNA-sequencing analysis on the fat bodies of wild-type and period clock gene null mutant larvae revealed circadian rhythms in the transcriptome of wild-type larvae. Surprisingly, period mutant exhibited 12-h rhythms in the expression of numerous genes, particularly those involved in peroxisome function, lipid metabolism, and oxidative stress response. Consistent with these transcriptomic data, peroxisome biogenesis and activity demonstrated 12-h rhythms in period mutant fat bodies. Furthermore, levels of reactive oxygen species displayed inverse-phased rhythms to that of lipid peroxidation, with 24-h rhythms in wild-type and 12-h rhythms in period mutant fat bodies. Moreover, while daily fat storage levels in wild-type larvae remained constant, period mutants exhibited fluctuations with a 12-h period and a net reduction in body fat storage. Collectively, our results identified a clock-independent ultradian rhythms in lipid metabolism, which may contribute to maintaining the metabolic, energetic, and redox homeostasis essential for larval survival and development.

2024-12-19 | GSE282559 | GEO

Non-alcoholic steatohepatitis disrupts diurnal liver transcriptome rhythms in mice

Project description:Circadian profiling improves target gene detection and pathway characterization in mouse models of NASH. Fatty livers show 3-hour advances in metabolic and clock gene transcript rhythms. Circadian profiling further reveals temporal changes in lipid, carbohydrate, and cholesterol metabolic transcripts.

2023-06-16 | GSE217492 | GEO

Loss of PPARα function promotes epigenetic dysregulation of lipid homeostasis driving ferroptosis and pyroptosis lipotoxicity in Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) [MouseMethylation]

Project description:Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is a growing epidemic with an estimated prevalence of 20‑30% in Europe and the most common cause of chronic liver disease worldwide. The onset and progression of MASLD are orchestrated by an interplay of the metabolic environment with genetic and epigenetic factors. Emerging evidence suggests altered DNA methylation pattern as a major determinant of MASLD pathogenesis coinciding with progressive DNA hypermethylation and gene silencing of the liver‑specific nuclear receptor PPARα, a key regulator of lipid metabolism. To investigate how PPARα loss of function contributes to epigenetic dysregulation in MASLD pathology, we studied DNA methylation changes in liver biopsies of WT and hepatocyte‑specific PPARα KO mice, following a 6‑week CDAHFD (choline-deficient, L-amino acid-defined, high-fat diet) or chow diet. Interestingly, genetic loss of PPARα function in hepatocyte‑specific KO mice could be phenocopied by a 6-week CDAHFD diet in WT mice which promotes epigenetic silencing of PPARα function via DNA hypermethylation, similar to MASLD pathology. Remarkably, genetic and lipid diet‑induced loss of PPARα function triggers compensatory activation of multiple lipid sensing transcription factors and epigenetic writer-eraser-reader proteins, which promotes the epigenetic transition from lipid metabolic stress towards ferroptosis and pyroptosis lipid hepatoxicity pathways associated with advanced MASLD. In conclusion, we show that PPARα function is essential to support lipid homeostasis and to suppress the epigenetic progression of ferroptosis‑pyroptosis lipid damage associated pathways towards MASLD fibrosis.

2024-03-01 | GSE238173 | GEO

Identifying PTMs on PERIOD over a circadian day in Drosophila melanogaster

Project description:Circadian clocks coordinate time-of-day specific metabolic and physiological processes to maximize performance and fitness. In addition to light, which is considered the strongest time cue to entrain animal circadian clocks, metabolic input has emerged as an important signal for clock modulation and entrainment, especially in peripheral clocks. Circadian clock proteins have been to be substrates of O-GlcNAcylation, a nutrient sensitive post-translational modification (PTM), and the interplay between clock protein O-GlcNAcylation and other PTMs, like phosphorylation, is expected to facilitate the regulation of circadian physiology by metabolic signals. Here, we used mass spectrometry proteomics to identify PTMs on PERIOD, the key biochemical timer of the Drosophila clock, over the circadian cycle.

2017-11-23 | MSV000081736 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data