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Human HNF4A Protein expressed in HEK-293 Cells - ABIN2722902
Ning, Koh, Pan, Jeong: Hepatocyte nuclear factor (HNF) 4α transactivation of cytochrome P450 (Cyp) 2d40 promoter is enhanced during pregnancy in mice. dans Biochemical pharmacology 2015
establish dHNF4 as a regulator of the adult metabolic state
Here the authors report that loss of Drosophila HNF4 recapitulates hallmark symptoms of Maturity Onset Diabetes of the Young 1 (MODY1), including adult-onset hyperglycemia, glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS).
Drosophila HNF4 mutants display diabetic phenotypes similar to those of sir2 mutants, and protein levels for dHNF4 are reduced in sir2 mutant animals. Sir2 exerts these effects by deacetylating and stabilizing dHNF4 through protein interactions.
Results support a feed-forward model for dHNF4, in which fatty acids released from triglycerides activate the receptor, inducing enzymes that drive fatty acid oxidation for energy production.
HNF4A acts redundantly with an intestine-restricted HNF4 paralog, HNF4G, to activate enhancer chromatin and upregulate the majority of transcripts in the differentiated epithelium; cells fail to differentiate on double knockout of both HNF4 paralogs. Furthermore, we show that SMAD4 and HNF4 function via a reinforcing feed-forward loop.
HNF4alpha binds the CSAD proximal promoter and induces CSAD transcription.
In mouse model of high fat diet-induced fatty liver oxidative stress impairs function of HNF4alpha on ApoB expression and VLDL secretion via PKC activation, eventually promoting fat accumulation in the liver.
HNF4A strongly transrepresses the transcriptional activity of the CLOCK:BMAL1 heterodimer.
These results indicate that PGC1alpha is involved in Acmsd expression through cooperation with HNF4alpha.
the tight conjunction of G4s and an adjacent stem-loop within the Hnf4a1 5' UTR was both necessary and sufficient to mediate the very strong translational repression.
PRMT1 inhibition, such as induced by alcohol, may result in epigenetic changes leading to loss of Hnf4alpha. This effect may contribute to alcohol's ability to promote liver tumors
this study shows that diabetes-linked transcription factor HNF4alpha regulates maminotransferase 2etabolism of endogenous methylarginines and beta-aminoisobutyric acid by controlling expression of alanine-glyoxylate
These results indicate a critical and conserved role for HNF4A in maintaining intestinal homeostasis in response to microbiota.
HNF4alpha is required for recruitment of the HDAC3-PROX1 module in liver.
In summary, HNF4alpha isoforms perform non-redundant functions in the colon under conditions of stress, underscoring the importance of tracking them both in colitis and colon cancer.
Hnf4alpha silencing with shRNA transfection into auditory neuroblast cells (VOT-33) reduced cell viability
both iron-dextran injection and a 3% carbonyl iron-containing diet led to upregulation of hepatic inflammation, which was associated with a significant reduction in HNF4alpha expression and its downstream target, miR-122.
Tg737 regulates a Wnt/beta-catenin/Snail-HNF4alpha negative feedback circuit, thereby blocking EMT and the malignant transformation of liver stem cells to liver cancer stem cells.
Down regulation of HNF4 alpha plays a role in metabolic liver function and the pathogenesis of liver cancer.
A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4alpha were ectopically expressed by adenoviral infection. We demonstrate the expression of CDX2 and HNF4alpha in human biopsy samples.
Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4alpha transcriptional network mediated through the Rho/Rho-associated protein kinase pathway.
key role in controlling hepatic CES2 expression in diabetes, obesity, or nonalcoholic steatohepatitis
These findings reveal a novel HNF4alpha network controlled by miR-194/192 that may play a critical role in maintaining the hepatocyte-differentiated state by inhibiting expression of genes involved in dedifferentiation and tumorigenesis.
HNF4alpha regulates homeostatic proliferation in the gastric epithelium and is both necessary and sufficient for the upstream regulation of the Xbp1-->Mist1 axis in maintenance of zymogen cell secretory architecture.
Results suggest that the cooperation of G4 and the adjacent putative protein-binding sites within the HNF4A 5' UTR was necessary and sufficient to mediate a strong translational repression. G4 motifs in the 5' UTRs of other liver-enriched transcription factors also inhibited protein expression. Moreover, pyridostatin, a G4 ligand, specifically potentiated the translational suppressing effect of P1-HNF4A-5' UTR.
insulin-positive cells can be generated in vitro from human induced pluripotent stem cells derived from patients carrying a non-sense HNF4A mutation, proving for the first time, that a human HNF4A mutation is neither blocking the expression of the insulin genes nor the development of insulin-producing cells in vitro
In 263 Japanese partients with suspected maturity-onset diabetes of the young, mutations were identified in 103 (39.2%) patients: 57 mutations in GCK; 29, HNF1A; 7, HNF4A; and 10, HNF1B.
Data report for the first time that HNF4 is a novel binding partner for Brg1. HNF4 recruits Brg1 to the Cyp3a11 promoter and formed a complex with Brg1 to trans-activate Cyp3a11.
HNF-4alpha contributes to the differentiation of WB-F344 cells into hepatocytes.
MODY mutations are loss-of-function mutations and HNF4alpha dimerization is essential for its optimal function and normal physiology.
heterogeneous clinical phenotypes of hyperinsulinism
Our and other data predict that the urate-raising T allele of rs1967017 enhances HNF4A binding to the PDZK1 promoter, thereby increasing PDZK1 expression. As PDZK1 is a scaffold protein for many ion channel transporters, increased expression can be predicted to increase activity of urate transporters and alter excretion of urate.
The prevalence of HNF1A mutation was relatively lower in Mainland China and HNF4A mutation was rare in a population of maturity-onset diabetes of the Young.
Maturity Onset Diabetes of the Young due to Glucokinase, HNF1-A, HNF1-B, and HNF4-A Mutations in a Cohort of Turkish Children Diagnosed as Type 1 Diabetes Mellitus.
Authors conclude that the HNF4alpha-SULT2B1b-CS axis represents a key endogenous mechanism to prevent uncontrolled gluconeogenesis.
Hepatocyte nuclear factor 4alpha directly regulates NHE3 promoter activity and its basal expression in the intestine.
Study demonstrates that TRIB1 suppression and TRIB1 overexpression respectively reduce and increase HNF4A activity. TRIB1 and HNF4A partially colocalize and form complexes in vivo. Mapping of the interaction interfaces identified two distinct regions within TRIB1 which associated with the N-terminal region of HNF4A. These findings establish that TRIB is required for HNF4A function.
The two isoforms of HNF4Alpha, which are differentially expressed in liver cancer, exhibit distinct circadian roles.
genetic association studies in population of children in Japan: Data suggest that mutations in INS, HNF1A, HNF4A, and HNF1B likely play critical roles in children with insulin-requiring autoantibody-negative type 1 diabetes in the population studied. (INS = insulin; HNF1A = HNF1 homeobox A; HNF4A = hepatocyte nuclear factor 4 alpha; HNF1B = HNF1 homeobox B)
Our findings highlight the regulatory networks among TFs, lncRNAs, miRNAs, and mRNAs in hepatocellular carcinoma (HCC). Several key molecules, such as hsa-miR-195, lncRNA MALAT1 and TFs TAF1 and HNF4alpha, may contribute to the progression of HCC.
Of the 465,447 CpG sites analyzed, 12 showed differential methylation (false discovery rate <0.15), including markers within genes associated with monogenic diabetes (HNF4A) or obesity (RREB1). The overall methylation at HNF4A showed inverse correlations with mRNA expression levels, though non significant
DDX3 regulates MTP gene expression and lipid homeostasis through interplay with HNF4 and SHP.
These findings suggest that GATA6 might interact with HNF4alpha and contribute to the development of mucinous-type lung adenocarcinomas
HNF4-alpha and particularly SATB2 may be helpful in the differential diagnosis of pulmonary adenocarcinoma and metastases of colorectal adenocarcinomas
HNF4 positively regulates pUPII gene promoter activity.
Tetra-primer ARMS-PCR identifies the novel genetic variations of bovine HNF-4alpha gene associating with growth traits.
Results show that chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-4gamma regulate growth hormone receptor 1A promoter activity through binding to a common DNA element
The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms.
hepatocyte nuclear factor 4 alpha
, hepatocyte nuclear factor 4, alpha
, hepatocyte nuclear factor 4-alpha-like
, hepatocyte nuclear factor 4-alpha
, hepatocyte nuclear factor 4
, hepatocyte nuclear factor 4 homologue
, HNF4 alpha
, Nuclear receptor 2A1
, nuclear receptor subfamily 2 group A member 1
, transcription factor 14
, transcription factor HNF-4
, alpha transcription factor 4
, hepatic nuclear factor 4, alpha
, hepatic nuclear factor 4 alpha
, hepatic nuclear factor 4
, hepatic nuclear factor 4alpha
, nuclear receptor