Lysine 117 residue is essential for the function of the hepatocyte nuclear factor 1α in pancreas
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PROVIDER: PRJNA971476 | ENA |
REPOSITORIES: ENA
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Project description:Hepatocyte nuclear factor 1α (HNF1α) play essential roles in controlling development and metabolism, its mutations are clearly linked to the occurrence of maturity-onset diabetes of the young (MODY3) in human. 117 lysine to glutamic acid (E117) mutation in the HNF1α gene was clinically associated with MOYD3, but no functional data on this variant is available. Here, we generated a knock-in mouse model in which the lysine 117 is replaced with glutamic acid in the endogenous murine HNF1α locus. The HNF1αE117/E117 mice reproduced HNF1-null phenotypes including dwarfism, hepatic dysfunction, renal Fanconi syndrome, diabetes and die from a progressive wasting syndrome, but no hyperphenylalaninemia. Moreover, HNF1αE117/E117 mice shared similar hepatic gene expression profiles with HNF1 deficient mice. In vitro experiments showed that HNF1 mutants in which the lysine 117 residue were replaced by glutamic acid, arginine or glutamine residues, respectively, had a significant decreased in overall transactivation and DNA binding capacity. K117 mutants had no effect on its protein stabilities and nuclear localization, but significantly blocked its own association. Our results clearly demonstrate that the lysine 117 residue is essential for the function of the HNF1a, and prove important to identify the molecular basis for diseases associated with defects in HNF1α We then performed gene expression profiling analysis using data obtained from RNA-seq of liver tissue of 3 WT mice and 3 KI mice.
2023-01-01 | GSE207758 | GEO
Project description:To determine the impact of K117E mutation on HNF1α functions, we generated a C57BL/6J knock-in mouse model wherein the lysine 117 (K117) was replaced with glutamic acid (E117) in the endogenous murine HNF1α locus by CRISPR/Cas9. We then performed gene expression profiling analysis using data obtained from RNA-seq of pancreas of WT and HNF1αK1117E Hom mice of 9 weeks old (n=3/group)
2023-11-23 | GSE232242 | GEO
Project description:Lysine 117 Residue is Essential for the Function of the Hepatocyte nuclear factor 1α
| PRJNA857016 | ENA
Project description:Although hepatocyte-nuclear-factor-1α (Hnf1α) is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions. Methodology/Principal Findings An Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway. Conclusions/Significance Together, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages. HNF1alpha was knocked out. A total of 3 control and 3 mutant littermate individuals were sacrificed at 4 months of age. The jejunum was harvested and total RNA was isolated from each individual. Each RNA sample was independently used to generate probes to screen Affymetrix chips.
2011-01-01 | E-GEOD-23040 | biostudies-arrayexpress
Project description:Cyanophage MED4-117 genome sequencing project
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Project description:Bradyrhizobium elkanii USDA 117 genome sequencing
| PRJNA834289 | ENA
Project description:biogas residue compost Raw sequence reads
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Project description:The β-adrenergic receptor signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β-AR activation highly induces transcriptional coactivator PGC-1α and its splice variant N-terminal (NT)-PGC-1α, promoting the transcription program of mitochondrial biogenesis and thermogenesis. In the present study, we evaluated the role of NT-PGC-1α in brown adipocyte energy metabolism by genome-wide profiling of NT-PGC-1α-responsive genes. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1α are highly enriched in mitochondrial pathways including fatty acid transport and β-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1α in the enhancement of mitochondrial function. Moreover, gene expression profiling of NT-PGC-1α revealed activation of distinct metabolic pathways such as glucose, lipid and nucleotide metabolism and of signaling pathways such as RAR and PPAR-γ/RXRα activation in brown adipocytes. Together, our data strengthen our previous findings that NT-PGC-1α is a key regulator of mitochondrial oxidative metabolism and thermogenesis in brown adipocytes and further suggest that NT-PGC-1α influences a broader spectrum of thermogenic processes to meet cellular needs for adaptive thermogenesis. Two samples from two groups: NT-PGC-1α overexpression and empty vector. There are technical replicates (A and B) for each group. Two RNA samples were pooled for each group.
2015-08-07 | E-GEOD-71774 | biostudies-arrayexpress