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The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis [glucacon/GW4064]

ABSTRACT: The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis [glucacon/GW4064]

PROVIDER: PRJNA451436 | ENA |

REPOSITORIES: ENA

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The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis [modulated FOXA2/FXR]

Project description:The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis [modulated FOXA2/FXR]

| PRJNA451493 | ENA

The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis [modulated FOXA2/FXR]

Project description:Identified genes deregulated in mouse primary hepatocytes after modulation of expression/activity of FOXA2 and FXR in glucagon or insulin state

2018-08-16 | GSE113549 | GEO

The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis

Project description:The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis

| PRJNA453136 | ENA

The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis [glucacon/GW4064]

Project description:Identified genes deregulated in mouse primary hepatocytes after glucagon and /or GW4064 treatment

2018-08-16 | GSE113526 | GEO

Pioneer factor Foxa2 mediates chromatin conformation changes in ligand-dependent activation of nuclear receptor FXR

Project description:Activation of nuclear receptors, a family of ligand-dependent transcription factors, is used extensively in development of drug targets. We have previously shown that pioneer factor Foxa2 opens chromatin for binding of nuclear receptors FXR and LXRα during acute ligand activation. FXR is activated by bile acids and deletion of Foxa2 in the liver results in intrahepatic cholestasis. We hypothesized that Foxa2 also enables chromatin conformational changes during ligand activation. We performed Foxa2 HiChIP to assess Foxa2-dependent long-range interactions in mouse livers treated with either vehicle control or FXR agonist GW4064. HiChIP contact analysis shows that global chromatin interactions are dramatically increased during FXR activation. Ligand-treated livers exhibit extensive redistribution of topological associated domains (TAD) and substantial increase in Foxa2-anchored loops, suggesting Foxa2 is involved in dynamic chromatin conformational changes. We demonstrate that chromatin conformation, including genome-wide interactions, TADs, intra-chromosomal and inter-chromosomal Foxa2-anchored loops, drastically changes upon addition of FXR agonist. Hence, we determine a novel role for Foxa2 in enabling these conformational changes, extending its function in bile acid metabolism.

2023-10-16 | GSE229049 | GEO

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

Development of gene expression signatures in the liver cancer cells with FXR overexpression and FXR activation

Project description:To investigate the role of nuclear receptor FXR during hepatocarcinogenesis, HepG2 cels and SK-Hep-1 cells were transfected with lentiviral mediated FXR overexpressive vector or the negative control. After the cells were treated with FXR agonist GW4064 2uM for 24 h, and total RNA were isolated for detection of gene expression .

2020-09-10 | GSE149111 | GEO

The nuclear Bile Acid Receptor FXR is a PKA- and FOXA2- sensitive Activator of Fasting Hepatic Gluconeogenesis

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

2018-08-16 | GSE113575 | GEO

Genome wide binding and transcriptome analysis of human FXR in primary human hepatocytes [HTS]

Project description:We report the genome-wide profiling of FXR binding by ChIP-seq from GW4064 or DMSO treated primary human hepatocytes. We reported altered RNA expression profiles in primary human hepatocypes upon GW4064 treatment compared to DMSO control by RNA-seq. We also reported the altered RNA expression profiles in livers from WT C57BL/6J mice upon GW4064 treatment compared to vehicle control. Primary human hepatocytes were treated with 5uM GW4064 or DMSO control, 1 hour later, cells were fixed and collected for chromatin isolation. 24 hours post treatment, cells were isolated for RNA isolation. This submission represents HTS component of study.

2014-07-24 | E-GEOD-57227 | biostudies-arrayexpress

Genome wide binding and transcriptome analysis of human FXR in primary human hepatocytes [HTS]

2014-07-24 | GSE57227 | GEO

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