Similar Datasets
Project description:Liver-specific matrin-3 knockout regulates hepatic transcriptome and chromatin accessibility in mice
| PRJNA1034149 | ENA
Project description:Matrin-3 is an RNA-binding protein involved in the pathogenesis of human diseases. Here we examined its previously uncharacterized role in regulating chromatin accessibility in the liver of mice. Bulk ATAC-seq and bioinformatics analysis identified 523 and 829 differential peaks (FDR < 0.05), respectively, in the liver of female mice fed a chow diet or 60% HFD for 16 weeks. Peak annotation by HOMER and ChIPseeker identified 183 and 444 genes, respectively, that are associated with the differential peaks. Enrichr analysis of these genes revealed that Hallmark terms such as "Xenobiotic metabolism" was enriched in the liver of chow-fed and HFD-fed mice. TRRUST database analysis from Metascape uncovered that Hnf4α is the main transcription factor regulating these peak-associated genes in the liver of chow-fed mice, and Hnf4α and Nr1i3 are the main transcription factors regulating these peak-associated genes in the liver of HFD-fed mice. Our data demonstrated that liver-specific matrin-3 deficiency alters chromatin accessibility likely affecting the action of two transcription factors Hnf4α and Nr1i3 in the liver of mice.
2024-10-01 | GSE246704 | GEO
Project description:Matrin-3 is an RNA-binding protein involved in the pathogenesis of human diseases. Here we examined the hepatic transcriptome of chow-diet fed mice. Bulk RNA-seq and bioinformatics analysis identified 646 and 145 differentially expressed genes (Padj < 0.05), respectively in the livers of female and male matrin-3 LKO mice. Enrichr analysis of these DEGs revealed several common Hallmark terms including cholesterol homeostasis, fatty acid metabolism, xenobiotic metabolism, and epithelial mesenchymal transition between female and male mice. Our data demonstrated that liver-specific matrin-3 deficiency re-programs the hepatic transcriptome in the liver of chow diet-fed mice.
2024-10-01 | GSE267224 | GEO
Project description:Matrin-3 is an RNA-binding protein involved in the pathogenesis of human diseases. Here we examined its previously uncharacterized role in limiting hepatic steatosis and stress response via the constitutive androstane receptor. Matrin-3 expression was induced in the steatotic livers of mice and humans. Liver-specific matrin-3 knockout (LKO) exacerbated high-fat diet (HFD)-induced steatosis, acute phase response, and inflammation in the liver of mice. Bulk RNA-seq and bioinformatics analysis identified 1,333 and 239 differentially expressed genes (fold change > 1.5 & Padj < 0.05), respectively in the livers of female and male matrin-3 LKO mice. Gene Set Enrichment Analysis revealed that the top most enriched Gene Ontology Biological Process was the “Xenobiotic metabolic process” in female matrin-3 floxed mice that is downregulated. The top two enriched biological processes are “Acute inflammatory response” and “Acute phase response” in the liver of female LKO mice that are upregulated. Several GO terms related to lipid metabolism and xenobiotic metabolism were enriched in the livers of male mice. Real-time qPCR revealed that the expression of many genes involved in xenobiotic metabolism was reduced in the liver of female LKO mice and to a lesser extent in the liver of male LKO mice, while the expression of acute-phase response genes was induced in the liver of female but not male LKO mice. Our data demonstrated that liver-specific matrin-3 deficiency re-programs the hepatic transcriptome enriched for xenobiotic metabolism pathway, acute-phase and inflammatory response signaling in the liver of HFD-fed mice.
2024-10-01 | GSE246706 | GEO
Project description:Canine copper toxicosis is an autosomal recessive disorder characterized by hepatic copper accumulation resulting in liver fibrosis and eventually cirrhosis. We have identified COMMD1 as the gene underlying copper toxicosis in Bedlington terriers. Although recent studies suggest that COMMD1 regulates hepatic copper export via an interaction with the Wilson disease protein ATP7B, its importance in hepatic copper homeostasis is ill-defined. In this study, we aimed to assess the effect of Commd1 deficiency on hepatic copper metabolism in mice. Liver-specific Commd1 knockout mice (Commd1(?hep)) were generated and fed either a standard or a copper-enriched diet. Copper homeostasis and liver function were determined in Commd1(?hep) mice by biochemical and histological analyses, and compared to wild-type littermates. Commd1(?hep) mice were viable and did not develop an overt phenotype. At six weeks, the liver copper contents was increased up to a 3-fold upon Commd1 deficiency, but declined with age to concentrations similar to those seen in controls. Interestingly, Commd1(?hep) mice fed a copper-enriched diet progressively accumulated copper in the liver up to a 20-fold increase compared to controls. These copper levels did not result in significant induction of the copper-responsive genes metallothionein I and II, neither was there evidence of biochemical liver injury nor overt liver pathology. The biosynthesis of ceruloplasmin was clearly augmented with age in Commd1(?hep) mice. Although COMMD1 expression is associated with changes in ATP7B protein stability, no clear correlation between Atp7b levels and copper accumulation in Commd1(?hep) mice could be detected. Despite the absence of hepatocellular toxicity in Commd1(?hep) mice, the changes in liver copper displayed several parallels with copper toxicosis in Bedlington terriers. Thus, these results provide the first genetic evidence for COMMD1 to play an essential role in hepatic copper homeostasis and present a valuable mouse model for further understanding of the molecular mechanisms underlying hepatic copper homeostasis.
| S-EPMC3245254 | biostudies-literature
Project description:Liver-specific matrin-3 knockout alters the chromatin accessibility in the liver of mice [ATAC-seq]
| PRJNA1034146 | ENA
Project description:ObjectivePARKIN is an E3 ubiquitin ligase that regulates mitochondrial quality control through a process called mitophagy. Recent human and rodent studies suggest that loss of hepatic mitophagy may occur during the pathogenesis of obesity-associated fatty liver and contribute to changes in mitochondrial metabolism associated with this disease. Whole-body Prkn knockout mice are paradoxically protected against diet-induced hepatic steatosis; however, liver-specific effects of Prkn deficiency cannot be discerned in this model due to pleotropic effects of germline Prkn deletion on energy balance and subsequent protection against diet-induced obesity. We therefore generated the first liver-specific Prkn knockout mouse strain (LKO) to directly address the role of hepatic Prkn.MethodsLittermate control (WT) and LKO mice were fed regular chow (RC) or high-fat diet (HFD) and changes in body weight and composition were measured over time. Liver mitochondrial content was assessed using multiple, complementary techniques, and mitochondrial respiratory capacity was assessed using Oroboros O2K platform. Liver fat was measured biochemically and assessed histologically, while global changes in hepatic gene expression were measured by RNA-seq. Whole-body and tissue-specific insulin resistance were assessed by hyperinsulinemic-euglycemic clamp with isotopic tracers.ResultsLiver-specific deletion of Prkn had no effect on body weight or adiposity during RC or HFD feeding; however, hepatic steatosis was increased by 45% in HFD-fed LKO compared with WT mice (P < 0.05). While there were no differences in mitochondrial content between genotypes on either diet, mitochondrial respiratory capacity and efficiency in the liver were significantly reduced in LKO mice. Gene enrichment analyses from liver RNA-seq results suggested significant changes in pathways related to lipid metabolism and fibrosis in HFD-fed Prkn knockout mice. Finally, whole-body insulin sensitivity was reduced by 35% in HFD-fed LKO mice (P < 0.05), which was primarily due to increased hepatic insulin resistance (60% of whole-body effect; P = 0.11).ConclusionsThese data demonstrate that PARKIN contributes to mitochondrial homeostasis in the liver and plays a protective role against the pathogenesis of hepatic steatosis and insulin resistance.
| S-EPMC7399260 | biostudies-literature
Project description:Liver-specific matrin-3 knockout alters the hepatic transcriptome of chow diet-fed mice [RNA-seq]
| PRJNA1110273 | ENA
Project description:Liver-specific matrin-3 knockout alters the hepatic transcriptome of high-fat diet-fed mice [RNA-seq]
| PRJNA1034150 | ENA
Project description:Xbp1 is an important regulator of unfolded protein response and lipid metabolism. Its dyregulation has been associcated in human NASH. Feeding a high fat diet with fructose/sucrose to mice causes progressive, fibrosing steatohepatitis. This study is to use RNA-Seq to identify differentially expressed genes in hepatic Xbp1 deficient mice livers fed with a high fat diet compared to controls. Hepatic Xbp1 deficient mice or flox controls were fed either regular chow or a high fat diet (n=4). Samples from each cohort were pooled into two replicates.
2016-01-07 | E-GEOD-64824 | biostudies-arrayexpress