Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nucleosome occupancy profiles in young and old mouse liver [MNase-Seq]

ABSTRACT: Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARα, PPARγ, and LXRα in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARα targets contributing to gene expression changes that lead to steatosis in aged liver.

ORGANISM(S): Mus musculus

PROVIDER: GSE58005 | GEO | 2014/10/23

SECONDARY ACCESSION(S): PRJNA248681

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver [ChIP-seq]

Project description:Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARα, PPARγ, and LXRα in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARα targets contributing to gene expression changes that lead to steatosis in aged liver. Genome-wide location analysis (ChIP-Seq) of Foxa2 and Hdac3 from young (3 months) and old (21 months) mouse livers

2014-10-23 | E-GEOD-60393 | biostudies-arrayexpress

Genome-wide expression profiles in young and old mouse liver [RNA-seq]

2014-10-23 | GSE57809 | GEO

Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver [ChIP-seq]

2014-10-23 | GSE60393 | GEO

Genome-wide expression profiles in young and old mouse liver [RNA-seq]

Project description:Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARÎ±, PPARÎ³, and LXRÎ± in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARÎ± targets contributing to gene expression changes that lead to steatosis in aged liver. Genome-wide expression profiles (RNA-Seq) from young (3 months) and old (21 months) mouse livers

2014-10-23 | E-GEOD-57809 | biostudies-arrayexpress

Nucleosome occupancy profiles in young and old mouse liver [MNase-Seq]

Project description:Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARM-NM-1, PPARM-NM-3, and LXRM-NM-1 in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARM-NM-1 targets contributing to gene expression changes that lead to steatosis in aged liver. Genome-wide nucleosome profiles (MNase-Seq) from young (3 months) and old (21 months) mouse livers

2014-10-23 | E-GEOD-58005 | biostudies-arrayexpress

Pioneer factor Foxa2 enables ligand-dependent activation of type II nuclear receptors FXR and LXRa

Project description:Type II nuclear hormone receptors, such as FXR, LXR, and PPAR, which function in glucose and lipid metabolism and serve as drug targets for metabolic diseases, are permanently positioned in the nucleus regardless of the ligand status. Ligand activation of these receptors is thought to occur by co-repressor/co-activator exchange, followed by initiation of transcription. However, recent genome-wide location analysis showed that LXRα and PPARα binding in the liver is largely ligand-dependent. We hypothesized that pioneer factor Foxa2 evicts nucleosomes to enable ligand-dependent receptor binding. We show that chromatin accessibility, FXR binding and LXRα occupancy, and ligand-responsive activation of gene expression by FXR and LXRα require Foxa2. Unexpectedly, Foxa2 occupancy is drastically increased when either receptor, FXR or LXRα, is bound by an agonist. In addition, co-immunoprecipitation experiments demonstrate that Foxa2 interacts with either receptor in a ligand-dependent manner, suggesting that Foxa2 and the receptor bind DNA as an interdependent complex during ligand activation. Furthermore, PPARα binding is induced in Foxa2 mutants treated with FXR and LXR ligands, leading to activation of PPARα targets.

2021-07-12 | GSE149075 | GEO

The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPARα

Project description:The class 3 phosphoinositide 3-kinase (PI3K) is required for the lysosomal degradation by autophagy and vesicular trafficking, assuring adaptation to energy shortages. Mitochondrial lipid catabolism is another important energy source. Autophagy and mitochondrial metabolism are transcriptionally controlled by nutrient sensing nuclear receptors. However, it is not known whether the class 3 PI3K contributes to this regulation. Here we show that hepatocyte-specific inactivation of Vps15, the essential regulatory subunit of the class 3 PI3K, results in mitochondrial depletion and a failure to oxidize fatty acids. Mechanistically, the transcriptional activity of Peroxisome Proliferator Activated Receptor alpha (PPARα), a nuclear receptor that orchestrates fatty acid catabolism, is blunted in Vps15-deficient livers. We find PPARα transcriptional repressors Histone Deacetylase 3 (Hdac3) and Nuclear receptor co-repressor 1 (NCoR1) accumulated in Vps15-deficient livers due to defective autophagic flux. Pharmacologic activation of PPARα with a synthetic ligand, re-expression of its co-activator Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α) or inhibition of Hdac3 restored mitochondrial biogenesis and lipid oxidation in Vps15-deficient hepatocytes. These findings reveal a role for the class 3 PI3K and autophagy in transcriptional coordination of mitochondrial metabolism.

2020-02-06 | E-MTAB-7685 | biostudies-arrayexpress

Identification of transcriptional changes due to loss of Hdac3 in liver at P17 and P28

Project description:Histone deacetylase 3 (Hdac3) is the enzymatic component of transcriptional repression complexes recruited by the nuclear hormone receptors. Inactivation of Hdac3 in cancer cell lines triggered apoptosis, and removal of Hdac3 in the germ-line of mice caused embryonic lethality. Therefore, we conditionally deleted the Hdac3 allele in the mouse liver. These mice developed hepatomegaly, which was the result of hepatocyte hypertrophy, and these morphological changes coincided with significant imbalances between carbohydrate and lipid metabolism. Loss of Hdac3 triggered changes in gene expression consistent with inactivation of repression mediated by nuclear hormone receptors. Mechanistically, loss of Hdac3 increased the levels of Pparγ2, and treatment of these mice with a Pparγ antagonist partially reversed the lipid accumulation in the liver. In addition, gene expression analysis identified mTOR (mammalian target of rapamycin) signaling as being activated by deletion of Hdac3, and inhibition by rapamycin also affected the accumulation of neutral lipids in the Hdac3-null livers. Thus, Hdac3 has a key role in regulation of multiple signaling pathways in the liver, and deletion of Hdac3 disrupts normal metabolic homeostasis. Keywords: Genetic knockout of Hdac3 specifically in liver, and RNA analyzed from postnatal day 17 or 28 livers for transcriptional changes related to the given phenotypes

2008-05-22 | GSE10503 | GEO

Global quantitative proteomics of mouse brain structures reveals significant alterations in expression of proteins involved in neuronal plasticity during aging

Project description:Aging is believed to be the result of alterations of protein expression and accumulation of changes in biomolecules. Although there are numerous reports demonstrating changes in protein expression in brain during aging, only few of them describe global changes in the protein level. Here, we present a deepest quantitative proteomic analysis of three brain regions, hippocampus, cortex and cerebellum, in mice aged 1 and 12 months, using the total protein approach technique. In all the brain regions, both in young and in middle-aged animals, we identified over 6,700 proteins. We found that although the total protein expression in middle-aged brain structures is practically unaffected by aging, there are significant differences between young adult and middle-aged mice in the expression of some receptors and signaling cascade proteins proven to be significant for learning and memory formation. Our analysis demonstrates that hippocampus is the most unstable structure during natural aging and that the first symptoms of weakening of neuronal plasticity may be observed on protein level in middle-aged animals.

2018-07-03 | PXD009792 | Pride

Transcriptome analysis reveals key genes and pathways that the nuclear receptor PPARα acts on vascular aging

Project description:Our research is helpful to understand the physiological and pathological level changes caused by the nuclear transcriptional receptor PPARα acts on vascular aging, to find the mechanism of the signaling pathway downstream of PPARα in VSMCs, and to determine which signaling pathway is mediated by PPARα

2023-03-31 | GSE198045 | GEO

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