|
ORF cDNA clones
|
CRISPR / TALEN
|
Lentivirus
|
AAV
|
TALE-TF
|
ORF knockin clones
|
|
Antibody
|
Proteins
|
miRNA target clones
|
qPCR primers
|
shRNA clones
|
miRNA products
|
Promoter clones
|
Validated All-in-One™ qPCR Primer for HNF4A(NM_000457.4) Search again
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
Summary
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.
Gene References into function
- Control transcription of aldehyde dehydrogenase 2
- HNF4 alpha activates the insulin gene directly, through a previously unrecognized cis element
- HNF-4alpha is involved in regulating cancer cell transmigration by modulating the Fas-FasL system
- mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families.
- variation in the HNF4alpha enhancer element is not a common cause of susceptibility to type 2 diabetes
- MODY is caused by a translocation at chromosome 20, resulting in an upstream disruption of the gene
- spermine significantly enhanced the interaction between HNF4alpha and full-length DRIP205 in an AF-2, NR-box-dependent manner. Spermine enhanced the interaction of DRIP205 with the VDR , but decreased the interaction of both HNF4alpha and VDR with GRIP1
- These results support clinical findings that liver function can also be impaired in diabetic patients having hepatocyte nuclear factor 4alpha (HNF4alpha) mutations.
- cooperative role with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line
- The missense mutation was located in the DNA binding domain of HNF4A, and identification of this mutation allowed for presymptomatic diagnosis in the younger generations and will improve medical follow-up of the predisposed individuals.
- 2.7 A X-ray crystalography results suggest that the HNF4s may be transcription factors that are constitutively bound to fatty acids
- These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells.
- Maturity-onset diabetes of the young resulting from a novel mutation in the HNF-4alpha gene.
- the order of recruitment of factors to the HNF-4alpha regulatory regions upon the initial activation of the gene during enterocyte differentiation
- regulates transcription of hepatitis B virus
- Twenty different mutations in the HNF-4alpha, GCK and HNF-1alpha in 29 families. Three of 3, 10 of 11 and 1 of 6 of the mutations identified in HNF-4alpha, GCK and HNF-1alpha respectively, were new.
- Results suggest that the transcriptional cross talk between the TGFbeta-regulated Smads 3 and 4 and hepatocyte nuclear factor-4 is mediated by specific functional domains in the two types of transcription factors.
- HNF4 alpha isoforms originating from the P1 promoter exhibit stronger transcriptional activities and recruit coactivators more efficiently than isoforms driven by the P2 promoter.
- Transdifferentiation to the hepatocytic phenotype in hepatoid adenocarcinoma tissue of the stomach was not directly associated with HNF-4alpha expression, thus suggesting that transdifferentiation proceeds by a complicated mechanism.
- Hepatic expression of HNF-4 was impaired in advanced human cirrhosis and negatively correlated with WT1 mRNA levels
- hepatocyte nuclear factor-4 binds to SREBP2 to enhance sterol isomerase gene expression in hepatocytes
- HNF4-alpha, HNF3-beta and Sp1/Sp3 are important in regulation of prothrombin expression
- HNF-4alpha plays an important role in the differentiation and maintenance of the matured human hepatocyte phenotype.
- HNF-4alpha represents a potential modifier of the glycerol kinase deficiency phenotype
- HNF-4alpha has a role in regulating gluconeogenic genes along with PGC-1 and SREBP-1
- identifed systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II in liver and pancreatic islets; results suggest how misregulation of HNF4alpha can contribute to type 2 diabetes
- Human SNPs were identified across a 78-kb region around HNF4 alpha and evaluated in an association analysis of Ashkenazi Jewish type 2 diabetics and controls.
- A study population of Ashkenazi Jewish origin suggests that variant(s) located near or within HNF4A increases susceptibility to type 2 diabetes.
- residues of the ligand binding pocket are critical in hepatocyte nuclear factor-4alpha
- stimulated expression of the precore RNA and the core RNA from the core promoter of both the wild-type (WT) Hepatitis B virus and the double mutant, although its effect on the former was more prominent
- the V199I missense mutation located in the ligand binding/dimerization domain of HNF-4alpha contributes to type 2 diabetes in a Philippine-1 family
- ligand-activated PXR interferes with HNF-4 signaling by targeting the common coactivator PGC-1, which underlies physiologically relevant inhibitory cross-talk between drug metabolism and cholesterol/glucose metabolism
- HNF-4 and FXR, are closely involved in MTP gene expression, and the results provide evidence for a novel interaction between bile acids and lipoprotein metabolism.
- Data show that nitric oxide and transforming growth factor-beta1 inhibit hepatocyte nuclear factor-4alpha function in HEPG2 cells.
- HNF4alpha as a major factor for the control of UGT1A9 hepatic expression.
- Association of the HNF4alpha P2 promoter haplotype with type 2 diabetes in a U.K. Caucasian population where there is no evidence of linkage to 20q.
- HNF-4alpha is linked to late-onset type 2 diabetes.
- A comparision of gene expression patterns induced by hepatic nuclear factors, HNF6, HNF4alpha and HNF1beta, in a pancreatic beta- cell line.
- human microsomal triglyceride transfer protein is transcriptionally regulated by hepatocyte nuclear factor-4alpha
- Variants in both the P1 and P2 promoters of HNF4A increase risk for typical type 2 diabetes.
- Single nucleotide polymorphisms of HNF4-alpha associated with the risk of type 2 diabetes are evaluated.
- Among Ashkenazi Jewish subjects, variation near the P2 region of HNF4A is associated with type 2 diabetes in the Danish population.
- None of the previously associated SNPs confer an increased risk for diabetes in French Caucasians.
- In the present study, we investigated the expression of HNF4alpha in beta-cells and examined its functional properties.
- In this study, we evaluated 23 SNPs spanning 111 kb including the HNF4A gene for association with type 2 diabetes.
- Rare loss-of-function mutations in HNF4A cause maturity-onset diabetes common noncoding variants are associated with type 2 diabetes (review)
- role in regulating CYP7A1
- analysis of amino acids involved in coactivator and ligand interactions in hepatocyte nuclear factor-4alpha
- The HNF-4alpha clinical phenotype and beta cell dysfunction are similar to HNF-1alpha in maturity onset diabetes in the young.
- Cotransfection with an HNF-4alpha expression vector demonstrated a direct activation of the ALPI promoter through -94 to -82 element
- there is cross talk between distal CAR/PXR sites and HNF4alpha binding sites in the CYP2C9 promoter and that the HNF4alpha sites are required for maximal induction of the CYP2C9 promoter.
- relative prevalence of 3% of MODY1 (two different mutations in two families), 10% of MODY2 (seven in eight), and 36% of MODY3 (21 in 28) among Danish kindred clinically diagnosed as MODY
- role in transcriptional regulation of CYP2C8
- Expression of wild-type HNF4alpha but not of the mutants led to reduction of proliferation and alterations of cell morphology
- HNF-4alpha directly regulates human apoAV promoter through DR1 [a direct repeat separated by one nucleotide (nt)], and via a novel element for HNF-4alpha consisting of an inverted repeat separated by 8 nt (IR8).
- conclude that variants in hepatocyte nuclear factor 4alpha (HNF4alpha) do not appear to be major determinants for type 2 diabetes in Pima Indians but may have a minor role in genetic susceptibility
- HNF-1alpha-HNF-4alpha functional interactions are accomplished by regulating factor promoter occupancy and defective factor-factor interactions may contribute to the maturity onset diabetes of the young phenotype.
- E-cadherin controls enterocyte-specific expression of genes, such as the apoA-IV gene, through the control of hepatic nuclear factor 4alpha nuclear abundance
- This study demonstrates that p38 kinase-mediated Ser158 phosphorylation is essential for augmentation of the DNA binding and transactivation potential of HNF4alpha in the presence of IL-1beta+H2O2.
- Prox1 is a novel co-regulator of HNF4alpha that may play a key role in the regulation of bile acid synthesis and gluconeogenesis in the liver
- Mutations and phenotype heterogeneity in type 2 diabetes pedigrees.
- Polymorphisms in HNF-4alpha are not associated with type 2 diabestes and prediabetic phenotypes a Polish Caucasian study group..
- No mutation was identified in the HNF-4alpha genes in Japanese patients with juvenile-onset (before 18 years of age) non-obese diabetes mellitus.
- STAT5b and HNF4alpha exhibit bi-directional cross-talk that may augment HNF4alpha-dependent gene transcription while inhibiting STAT5b transcriptional activity via the inhibitory effects of HNF4alpha on JAK2 phosphorylation
- Possible existence of an a functional polymorphism in the P2 promoter region of the HNF4A gene that directly influences susceptibility to type 2 diabetes.
- a rare, novel mutation that disrupts a protein binding site in the pancreatic HNF4A promoter associates with late-onset diabetes
- study identified three novel HNF4A mutations and a 3.7-Mb haplotype, including the HNF4A P2 promoter, which was linked with diabetes
- Factors that trigger an NF-kappaB response in hepatic cells inhibit the transcriptional activity of HNF-4-dependent promoters; this inhibition could be accounted for by a decrease in DNA binding and the down-regulation of HNF-4.
- Common HNF4A variants are associated with high serum lipid levels and the metabolic syndrome.
- SNPs of HNF4A and their haplotypes predispose to type 2 diabetes mellitus in female subjects of the STOP-NIDDM study population.
- These results establish the importance of coactivators PGC1alpha and SRC1 for the hepatic expression of human P450s and uncover a new HNF4alpha-dependent regulatory mechanism to constitutively control the CYP1A1/2 cluster.
- HNF4A gene mutation is rare in Chinese pedigrees with early and/or multiplex-onset diabetes.
- HNF4alpha, CREM, HNF1alpha, and C/EBPalpha have roles in transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine
- the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1 alpha-mediated coactivation of HNF-4 alpha in addition to glucocorticoid-dependent actions
- Thirty-nine single nucleotide variations, including 16 novel ones, were found in the 5' promoter region, all of the exons and their surrounding introns of HNF4A in 74 Japanese type II diabetic patients.
- The results point to an absolute requirement of enhancer-promoter communication for maintaining the active state of the HNF-4 gene and provide evidence for a molecular bookmarking mechanism.
- Expression of Thy1 decreased in differentiated ADSC and BMSC. Expression of albumin, CYP2E1, and CYP3A4 increased in differentiated BMSC and ADSC. Hepatic gene activation may involve increased C/EBPbeta and HNF4alpha.
- Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters
- PRMT1 is a coactivator for HNF4, an orphan nuclear receptor that regulates the expression of genes involved in diverse metabolic pathways
- Results support the possibility that a variant in the P2 promoter region of HNF4A, or variants in linkage disequilibrium within this region, contributes to susceptibility to type 2 diabetes in many ethnic populations including Mexican Americans.
- hepatocyte nuclear factor 4alpha-mediated transcription from the human UGT1A9 promoter was discovered to be entirely dependent on hepatocyte nuclear factor 1.
- Transcriptional regulation of cripto-1 expression by WNT signaling through an intronic-exonic enhancer element, containing three tandem TCF/LEF binding sites within the CR-1 gene.
- These findings suggest that downregulation of P1 promoter-driven HNF4alpha expression is involved in tumor metastasis and a worse prognosis.
- Inflammatory-redox state enhances PC4-HNF4 binding to upregulate transcription of target hepatocyte genes, such as iNOS
- A study evaluating the extent to which common variation in the six known maturity-onset diabetes of the young (MODY) genes, which cause a monogenic form of type 2 diabetes, is associated with type 2 diabetes is presented.
- Studying genotype interactions of hFABP2 and HNF-4alpha, that are both candidate genes for diabetes type 2, may be a powerful approach.
- this paper reports the first characterization of the human OAT1 promoter and the first gene in the kidney whose promoter activity is regulated by HNF-4alpha
- HNF-4alpha expression is associated with the intestinal phenotype of non-neoplastic and neoplastic gastric glandular cells, suggesting an involvement in the establishment and maintenance of the intestinal phenotype of gastric mucosa and adenocarcinomas.
- Cooperative interaction between HNF4A and GATA4 and GATA6 regulates ABCG5 and ABCG8.
- HNF4A plays a key role in determining foetal birthweight.
- observations suggest that HNF4alpha1 positively regulates constitutive androstane receptor (CAR) expression in normal developing & adult livers, whereas HNF4alpha7 represses CAR gene expression in hepatocellu;lar carcinoma
- Our data suggest that the LBP gene may confer genetic susceptibility to T2D and this warrants further replication study.
- HNF4A variants identified so far appear to modestly contribute to predisposition for type 2 diabetes.
- HNF-4alpha is a crucial mediator in the regulation of alpha1-antitrypsin, transthyretin, and apolipoprotein B gene expression
- interindividual variation in the expression level of HNF4A probably determines variation in expression and activity of a broad scope of xenobiotic metabolism genes
- CYP3A4 enhancers co-ordinate the proximal promoter in responding similarly to the pregnane X receptor but differentially to hepatocyte nuclear factor-4alpha
- Re-expression of E-cadherin in HT29(US) cells restored the ability of caveolin-1 to down-regulate beta-catenin-Tcf/Lef-dependent transcription and survivin expression, as seen in HT29(ATCC) cells.
- Variation in the HNF4A region is associated with type 2 diabetes in Scandinavians.
- HNF4alpha plays a dominant role in the expression of drug-metabolizing enzymes and transporters
- Inter-individual/inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of HNF4A cannot account for this variability.
- Results suggest a general model by which a differentiation factor (HNF4alpha1) and a proliferation factor (c-Myc) may compete for control of genes involved in cell proliferation and differentiation.
- Macrosomia and neonatal hypoglycaemia in RW pedigree subjects with a mutation (Q268X) in the gene encoding hepatocyte nuclear factor 4alpha.
- TGFbeta1 represses CYP7A1 gene transcription in human hepatocytes by a mechanism involving Smad3-dependent inhibition of HNF4alpha and histone deacetylase remodeling of CYP7A1 chromatin.
- HNF4alpha primarily regulatea both growth and function of islet beta-cells. [REVIEW]
- Cited2, a coactivator of HNF4alpha, is essential for liver development
- HNF-4alpha plays a crucial role in human PZ gene expression in hepatocytic cells, and Sp1 is also important
- HNF1alpha and HNF4alpha are the factors involved in the interindividual variability of liver UGT1A6 and UGT1A9 mRNA expression.
- Data show that HNF-4alpha is developmentally regulated in the human liver: HNF-4alpha2 and HNF-4alpha8 are expressed in fetal hepatocytes but only HNF-4alpha2 is expressed in postnatal liver.
- monosaccharide-induced lipogenesis reduced hepatic HNF-4alpha levels, which in turn attenuated SHBG expression.
- high frequency of the HNF4A T130I variant in our population & its association to early-onset type 2 diabetes(T2D)& the risk for premature chronic complication suggest an important role of this variant in the pathogenesis of T2D in the Mexican population
- Variation in PPARG2 and HNF4A may interact to regulate insulin sensitivity in Mexican Americans at risk for type 2 diabetes.
- 14 of 56 HNF4 alpha-regulated genes, including well-known cancer genes, are able to contribute to the inhibitory effect of HNF4 alpha on cell proliferation
- Dysregulation of HNF 4 alpha and TRPC1 may be a possible molecular rationale in diabetic nephropathy.
- Regulation of vascular endothelial growth factor D by hepatocyte nuclear factor-4 alpha and chicken ovalbumin upstream promoter transcription factors 1 and 2.
- The nuclear hormone receptors hepatocyte nuclear factor 4 (HNF4) and retinoid X receptor alpha (RXRalpha) support hepatitis B virus (HBV) pregenomic RNA synthesis and viral replication in nonhepatoma cells.
- Macrosomic infants with transient or persistent hyperinsulinemic hypoglycemia should be screened for HNF4A mutations if there is a family history of youth-onset diabetes.
- In this review, HNF4 alpha controls constitutive expression of many hepatic genes but under certain circumstances can be subjected to regulation by differential co-activator recruitment, by phosphorylation and by interaction with other nuclear receptors.
- A knock-down of hepatocyte nuclear factor 4alpha significantly decreased expression levels of endogenous pregnane X receptor in HepG2 tumor cells.
- Data show that a concerted action of HNF4alpha and HNF1alpha, which also determines morphological and functional differentiation of hepatocytes, links HBV replication to hepatocyte differentiation.
- isoforms of the HNF4A P1 promoter are expressed in human fetal, but not adult, pancreas, and their presence during pancreatic development may moderate the diabetic phenotype in mutations in the HNF4A gene.
- In order to elucidate the molecular basis of HNF4 function in maturity onset diabetes of the young, an HNF4 DNA-binding domain is presented in complex with a high-affinity HNF1 promoter element containing the HNF4 recognition sequence.
- TASP1, EPS15R, and PRPF3 expression were significantly induced in HCCs of transgenic EGF2B mice as was P2 promoter-driven HNF4alpha
- HNF4alpha regulates thyroid hormone homeostasis through transcriptional regulation of the Dio1 gene with GATA4 and KLF9
- HNF4alpha directly interacts with the hHSS promoter region -209/-204 in vivo and strongly represses hHSS expression.
- The coactivator NCOA6 mediates the mechanism of the synergistic activation of the CYP2C9 gene by CAR and HNF4alpha.
- HNF4alpha9 & HNF4alpha3 were expressed in human Hep 3B hepatocellular carcinoma cells.
- SNP rs1884614 in the P2 promoter region of the HNF-4alpha gene may influence insulin secretion in non-obese Japanese subjects with type 2 diabetes.
- Human subjects with the HNF4A G60D genotype tended to have lower CYP2D6 activity than those with the wild-type HNF4A. The HNF4A G60D variant was detected at low frequency in Asian populations and was not found in Africans or Caucasians.
- Data indicate that the risk conferred by HNF4A P2 is significantly different between U.K. and Ashkenazi populations (P < 0.00007), suggesting that the underlying causal variant remains unidentified.
- COUP-TFII antagonizes the repression of the PED/PEA-15 gene by HNF-4alpha.
- HNF-4 and Foxo1 are required for reciprocal transcriptional regulation of glucokinase and glucose-6-phosphatase genes in response to fasting and feeding
- Structural basis of natural promoter recognition by a unique nuclear receptor, HNF4alpha. Diabetes gene product.
- HNF4 alpha is demonstrated to be a useful marker for histological and cytological diagnosis of ovarian mucinous tumors.
- The possibility of the reversion of dedifferentiated hepatocarcinoma phenotype by means of HNF4a expression confirms the important role of this factor in the coordination of proliferation, differentiation and the maintenance of epithelial morphology.
- increased transcriptional activity of HNF-4 converging onto genes coding for antiapoptotic oncogenes and cytokines may promote CRC development.
- Hepatocyte nuclear factor 4alpha (HNF4alpha) isoform and progesterone receptor were expressed in pancreatic alpha-cells, but not beta-cells in the human pancreas.
