Hepatocyte nuclear factor 4 (HNF-4), a highly conserved member of the steroid hormone receptor superfamily critical for development and liver-specific gene expression, is very similar to another superfamily member, retinoid X receptor alpha (RXR alpha), in overall amino acid sequence and DNA binding specificity. Since RXR alpha is known to heterodimerize with many other nuclear receptors, the f...

There is still relatively limited information about mechanisms of gene expression in enterocytes and mechanisms by which gene expression is regulated during enterocyte differentiation. Using the human intestinal epithelial cell line Caco-2, which spontaneously differentiates from a cryptlike to a villouslike enterocyte, we have previously shown that there is a marked increase in transcription o...

Hu, Chaobin, and David H. Perlmutter. Regulation of a1-antitrypsin gene expression in human intestinal epithelial cell line Caco-2 by HNF-1a and HNF-4. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G1181–G1194, 1999.— There is still relatively limited information about mechanisms of gene expression in enterocytes and mechanisms by which gene expression is regulated during enterocyte di...

PHYSIOLOGIC ROLE OF HNF-3 IN MOUSE LIVER AND PANCREATIC FUNCTION 63 Transcriptional Activity of the HNF-3 Proteins 63 Potential HNF-3 Target Genes in the Liver 63 Cellular Expression Pattern of HNF-3 Isoforms in Mouse Development and Adult Organs 63 The HNF-3β Gene Is Critical for Early Embryonic Development 65 Elevated Levels of HNF-3β in Mouse Hepatocytes Influence Expression of Genes Involve...

SHP (small heterodimer partner; NR0B2) is an atypical orphan NR (nuclear receptor) that functions as a transcriptional co-repressor by interacting with a diverse set of NRs and transcriptional factors. HNF-6 (hepatocyte nuclear factor-6) is a key regulatory factor in pancreatic development, endocrine differentiation and the formation of the biliary tract, as well as glucose metabolism. In this ...

Glucokinase (GK) is a key enzyme for glucose utilization in liver and shows a higher expression in the perivenous zone. In primary rat hepatocytes, the GK gene expression was activated by HNF (hepatic nuclear factor)-4alpha via the sequence -52/-39 of the GK promoter. Venous pO2 enhanced HNF-4 levels and HNF-4 binding to the GK-HNF-4 element. Thus, HNF-4alpha could play the role of a regulator ...

Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 proteins bind to DNA as monomers through a winged-helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic fork head (fkh) protein. We have previously characterized a strong-...

Defects in pancreatic -cell function contribute to the development of type 2 diabetes, a polygenic disease that is characterized by insulin resistance and compromised insulin secretion. Hepatocyte nuclear factors (HNFs) -1 , -3 , -4 , and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in -cell development and function. In mice, a heterozygous muta...

Vitamin D3 (1) is metabolized by various cytochrome P450 (CYP) enzymes, resulting in the formation of diverse metabolites. Among them, 4α,25-dihydroxyvitamin (6a) and 4β,25-dihydroxyvitamin (6b) are both produced from 25-hydroxyvitamin (2) CYP3A4. However, 6b detectable serum, whereas 6a not. We hypothesized that reason for this a difference susceptibility to CYP24A1-mediated metabolism. Here, ...