Similar Datasets
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
Project description:Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and -defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-κB but blocked that with RXRα, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXRα target genes. A dysregulated Acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders. FXR-WT or the FXR-K217Q mutant was expressed in lean mice and FXR-WT or the FXR-K217R mutant was expressed in obese mice by adenoviral infection. One week after infection, mice were treated with GW4064 (30 mg/kg in corn oil) overnight before sacrifice and hepatic expression was analyzed by Illumina microarray.
2014-10-17 | E-GEOD-62414 | biostudies-arrayexpress
Project description:The purpose of the present study was to explore in liver cells the connectivity that operates between three nuclear receptors in the liver, LXR, FXR, and PPARa, all three known to act on lipid and glucose metabolism, and also on inflammation. The human cell line HepaRG was selected for its proximity to human primary hepatocytes. Global gene expression of differentiated HepaRG cells was assessed after 4 hours and 24 hours of exposure to GW3965 (LXR agonist), GW7647 (PPARα agonist), and GW4064 and CDCA (FXR synthetic and natural agonist, respectively).
2019-06-27 | GSE124053 | GEO
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.
2014-07-24 | GSE57227 | GEO
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
Project description:FXR ChIP-seq was performed using the liver from adult male C57Bl6 mice
2016-10-13 | GSE87866 | GEO
Project description:Expression profiling of whole body (WB) FXR knockout (KO) mice (FXR WB KO), liver-specific FXR KO mice (AFXR Cre+) and enterocyte specific FXR KO mice (VFXR Cre+) on a C57BL/6J genetic background Whole body (WB) FXR knockout (KO) mice (FXR WB KO), liver-specific FXR KO mice (AFXR Cre+) and enterocyte specific FXR KO mice (VFXR Cre+) on a C57BL/6J genetic background were bred and maintained in the laboratory animal research facility at the University of Kansas Medical Center in rooms under a 12-hour light-dark cycle. All experiments used 10-16 week-old male mice. FXR was activated by treatment with the FXR synthetic agonist, GW4064, at 150 mg/kg. GW4064 or vehicle was administered by oral gavage at 6 p.m., followed by a second administration at 8 a.m. the next morning. Two hours later, the liver was harvested.
2014-01-31 | E-GEOD-54557 | biostudies-arrayexpress
Project description:The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids that regulates metabolic processes. FXR is expressed as four isoforms (α1-4), and their relative abundance is specific to tissue and bio-energetic conditions (Correia JC et al. 2015). Depending on the FXR isoform expressed, there is a degree of selectivity in target-genes activation. However, there is currently no data on how isoform-linked target selectivity is achieved. In this study we investigate the DNA binding profile of FXR isoforms on mouse liver organoids treated briefly with the FXR agonist obeticholic acid (OCA). From this analysis we concluded that FXR isoforms α2 and α4 binds to additional DNA regions, enriched for a specific discriminating binding motif. This binding led to isoform-selective gene regulation. Therefore, DNA binding selectivity therefore plays a defining role in FXR isoform-specific effects.
2020-07-27 | GSE133700 | GEO
Project description:The Farnesoid-X-Receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with Retinoid-X-Receptor (RXR). FXR is expressed as four isoforms (α1-α4) that drive transcription from IR-1 (inverted repeat-1) DNA motifs. More recently, FXR isoforms α2/α4 were found to activate transcription predominantly from non-canonical ER-2 (everted repeat-2) DNA motifs, mediating most metabolic effects of general FXR activation.Here, we explored whether co-occupancy of FXR and RXR in the mouse liver has an influence on DNA motif binding preference. We found RXR acts as a molecular switch, promoting FXRα2 activation from IR-1 instead of ER-2 motifs. Our results showcase FXR as the first NR with RXR-dependent and independent modes of activation, highlighting a potential new layer of complexity for other RXR-heterodimerizing NRs.
2024-03-20 | GSE261901 | GEO