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Angela L Tyner - One of the best experts on this subject based on the ideXlab platform.

  • hnf 1 alpha and hnf 1 beta expression in mouse intestinal crypts
    American Journal of Physiology-gastrointestinal and Liver Physiology, 1993
    Co-Authors: Michael S Serfas, Angela L Tyner
    Abstract:

    Hepatocyte Nuclear Factors 1 alpha and 1 beta (HNF-1 alpha and HNF-1 beta) are homologous homeodomain-containing transcription Factors that form homodimers or heterodimers that bind the same consensus sequence in the promoters of several genes expressed in liver. Many of these genes, including the mouse alpha-fetoprotein (AFP) gene, are also expressed in the intestinal epithelium. AFP expression is restricted to the enteroendocrine cell lineage in the adult small intestine, and we have investigated the distribution of HNF-1 alpha and HNF-1 beta mRNA in the mouse intestine to determine whether expression of either of these regulatory Factors colocalizes with AFP. We found that transcripts encoding both Factors are expressed at the highest levels in crypts of small and large intestine. Quantitation shows that the relative ratio of HNF-1 alpha to HNF-1 beta mRNAs appears lower in the colon, where AFP is not expressed. Alterations in the ratio of HNF-1 alpha to HNF-1 beta along the length of the intestine may influence HNF-1 dimer formation and expression of target genes. Although HNF-1 is necessary for transcription of the AFP gene, other Factors must be involved in eliciting the cell type-specific pattern of AFP expression in the intestine.

  • hnf 1α and hnf 1β expression in mouse intestinal crypts
    American Journal of Physiology-gastrointestinal and Liver Physiology, 1993
    Co-Authors: Michael S Serfas, Angela L Tyner
    Abstract:

    Hepatocyte Nuclear Factors 1α and 1β (HNF-1α and HNF-1β) are homologous homeodoxin-containing transcription Factors that form homodimers or heterodimers that bind the same consensus sequence in the promoters of several genes expressed in liver. Many of these genes, including the mouse α-fetoprotein (AFP) gene, are also expressed in the intestinal epithelium. AFP expression is restricted to the enteroendocrine cell lineage in the adult small intestine, and we have investigated the distribution of HNF-1α and HNF-1β mRNA in the mouse intestine to determine whether expression of either of these regulatory Factors colocalizes with AFP

Ubiratan Fabres Machado - One of the best experts on this subject based on the ideXlab platform.

  • Hepatocyte Nuclear Factors 1α 4α and forkhead box a2 regulate the solute carrier 2a2 slc2a2 gene expression in the liver and kidney of diabetic rats
    Life Sciences, 2013
    Co-Authors: Aline Davidsilva, Helayne Soares De ,freitas, Maristela Mitiko Okamoto, Robinson Sabinosilva, Beatriz Dagord Schaan, Ubiratan Fabres Machado
    Abstract:

    Aims Solute carrier 2a2 (Slc2a2) gene codifies the glucose transporter GLUT2, a key protein for glucose flux in Hepatocytes and renal epithelial cells of proximal tubule. In diabetes mellitus, hepatic and tubular glucose output has been related to Slc2a2/GLUT2 overexpression; and controlling the expression of this gene may be an important adjuvant way to improve glycemic homeostasis. Thus, the present study investigated transcriptional mechanisms involved in the diabetes-induced overexpression of the Slc2a2 gene. Main methods Hepatocyte Nuclear Factors 1α and 4α (HNF-1α and HNF-4α), forkhead box A2 (FOXA2), sterol regulatory element binding protein-1c (SREBP-1c) and the CCAAT-enhancer-binding protein (C/EBPβ) mRNA expression (RT-PCR) and binding activity into the Slc2a2 promoter (electrophoretic mobility assay) were analyzed in the liver and kidney of diabetic and 6-day insulin-treated diabetic rats. Key findings Slc2a2/GLUT2 expression increased by more than 50% (P < 0.001) in the liver and kidney of diabetic rats, and 6-day insulin treatment restores these values to those observed in non-diabetic animals. Similarly, the mRNA expression and the binding activity of HNF-1α, HNF-4α and FOXA2 increased by 50 to 100% (P < 0.05 to P < 0.001), also returning to values of non-diabetic rats after insulin treatment. Neither the Srebf1 and Cebpb mRNA expression, nor the SREBP-1c and C/EBP-β binding activity was altered in diabetic rats. Significance HNF-1α, HNF-4α and FOXA2 transcriptional Factors are involved in diabetes-induced overexpression of Slc2a2 gene in the liver and kidney. These data point out that these transcriptional Factors are important targets to control GLUT2 expression in these tissues, which can contribute to glycemic homeostasis in diabetes.

Mark Hungchih Chen - One of the best experts on this subject based on the ideXlab platform.

  • Hepatocyte Nuclear Factors 1alpha 1beta and 3beta expressed in the gonad of tilapia oreochromis mossambicus
    Biochemical and Biophysical Research Communications, 2001
    Co-Authors: Weitung Huang, Hongyi Gong, Cliff Jifan Lin, Chingfeng Weng, Mark Hungchih Chen
    Abstract:

    Hepatocyte Nuclear Factors (HNFs) are upstream regulators of many liver-specific genes and are involved in many cellular functions in the body, but their existence, expression, and function in gonads are still poorly understood. Here we report on the first cloning of partial cDNAs of HNF-1alpha and -1beta and full HNF-3beta cDNA from a tilapia (Oreochromis mossambicus) liver cDNA library. The deduced amino acid sequence of tilapia HNF-3beta has a 90 to 96% identity with those of other fishes (dwarf gourami, medaka, and zebrafish), 74% with mammals (human, rat, and mouse), and 82% with Xenopus. RT-PCR detected IGF-I and -II and HNF-1alpha, -1beta, and -3beta in both liver and gonads and the identity of the PCR fragments was confirmed by PCR hybridization. Immunoprecipitation and Western blotting also detected all three HNF proteins in both liver and gonads. Expression of HNFs in the gonads of the tilapia suggests that multi-HNFs may form a cascade to regulate gonadal physiology in the bony fish.

Michael S Serfas - One of the best experts on this subject based on the ideXlab platform.

  • hnf 1 alpha and hnf 1 beta expression in mouse intestinal crypts
    American Journal of Physiology-gastrointestinal and Liver Physiology, 1993
    Co-Authors: Michael S Serfas, Angela L Tyner
    Abstract:

    Hepatocyte Nuclear Factors 1 alpha and 1 beta (HNF-1 alpha and HNF-1 beta) are homologous homeodomain-containing transcription Factors that form homodimers or heterodimers that bind the same consensus sequence in the promoters of several genes expressed in liver. Many of these genes, including the mouse alpha-fetoprotein (AFP) gene, are also expressed in the intestinal epithelium. AFP expression is restricted to the enteroendocrine cell lineage in the adult small intestine, and we have investigated the distribution of HNF-1 alpha and HNF-1 beta mRNA in the mouse intestine to determine whether expression of either of these regulatory Factors colocalizes with AFP. We found that transcripts encoding both Factors are expressed at the highest levels in crypts of small and large intestine. Quantitation shows that the relative ratio of HNF-1 alpha to HNF-1 beta mRNAs appears lower in the colon, where AFP is not expressed. Alterations in the ratio of HNF-1 alpha to HNF-1 beta along the length of the intestine may influence HNF-1 dimer formation and expression of target genes. Although HNF-1 is necessary for transcription of the AFP gene, other Factors must be involved in eliciting the cell type-specific pattern of AFP expression in the intestine.

  • hnf 1α and hnf 1β expression in mouse intestinal crypts
    American Journal of Physiology-gastrointestinal and Liver Physiology, 1993
    Co-Authors: Michael S Serfas, Angela L Tyner
    Abstract:

    Hepatocyte Nuclear Factors 1α and 1β (HNF-1α and HNF-1β) are homologous homeodoxin-containing transcription Factors that form homodimers or heterodimers that bind the same consensus sequence in the promoters of several genes expressed in liver. Many of these genes, including the mouse α-fetoprotein (AFP) gene, are also expressed in the intestinal epithelium. AFP expression is restricted to the enteroendocrine cell lineage in the adult small intestine, and we have investigated the distribution of HNF-1α and HNF-1β mRNA in the mouse intestine to determine whether expression of either of these regulatory Factors colocalizes with AFP

David J Waxman - One of the best experts on this subject based on the ideXlab platform.

  • growth hormone regulation of sex dependent liver gene expression
    Molecular Endocrinology, 2006
    Co-Authors: David J Waxman, Caitlin Oconnor
    Abstract:

    The liver is a primary target for the action of GH, a pituitary protein hormone that regulates a broad range of physiological processes, including long bone growth, fatty acid oxidation, glucose uptake, and hepatic steroid and foreign compound metabolism. GH exerts sex-dependent effects on the liver in many species, with many hepatic genes, most notably genes coding for cytochrome P450 (CYP) enzymes, being transcribed in a sex-dependent manner. Sex differences in CYP expression are most striking in rats and mice (up to 500-fold male-female differences), but are also seen, albeit to a much smaller degree, in humans, where they are an important determinant of the sex dependence of hepatic drug and steroid metabolism. This article examines the mechanisms whereby GH, via its sex-dependent temporal patterns of pituitary release, activates intracellular signaling leading to the sexually dimorphic transcription of CYPs and other liver-expressed genes. Recent findings implicating the GH-regulated transcription factor STAT5b (signal transducer and activator of transcription 5b), Hepatocyte Nuclear Factors 3beta, 4alpha and 6, and sex differences in DNA methylation and chromatin structure in the sex-dependent actions of GH are reviewed, and current mechanistic models are evaluated.

  • role of Hepatocyte Nuclear Factors in transcriptional regulation of male specific cyp2a2
    Journal of Biological Chemistry, 2005
    Co-Authors: Christopher A Wiwi, David J Waxman
    Abstract:

    Cytochrome P450 2A2 (CYP2A2) is an adult male-specific rat liver steroid hydroxylase whose sex-dependent expression is regulated at the transcriptional level by sexually dimorphic pituitary growth hormone (GH) secretory patterns. In contrast to CYP2C11 and other male-specific, plasma GH pulse-inducible liver genes, CYP2A2 is highly expressed in hypophysectomized rat liver, despite the absence of GH stimulation. CYP2A2 promoter fragments 0.9–6.2 kb long exhibited unusually high basal promoter activity when transfected into the liver cell line HepG2. A further ∼2.5-fold increase in activity was obtained by cotransfection of Hepatocyte Nuclear factor (HNF) 3γ or HNF4α. CYP2A2 promoter activity was inhibited ∼85% by transfection of HNF3β or HNF6, both of which are more highly expressed in female than male liver and can strongly trans-activate the female-specific CYP2C12 promoter. The male GH pulse-activated transcription factor STAT5b had no effect on CYP2A2 promoter activity, either alone or in combination with HNF3γ and HNF4α, consistent with the GH pulse-independence of CYP2A2 expression. By contrast, STAT5b synergistically enhanced the transcriptional activity of HNF4α toward two other male-specific liver target genes, Cyp2d9 and CYP8B1. Furthermore, STAT5b in combination with the HNF4α coactivator peroxisome proliferator-activated receptor γ coactivator-1α strongly enhanced the transcriptional activity of HNF4α toward CYP8B1 but not toward CYP2A2. These findings support the hypothesis that sex-dependent HNFs contribute to the sexually dimorphic expression of CYP2A2 and other liver CYPs and highlight the ability of STAT5b to act in concert with HNF4α to regulate select male-specific liver CYP genes.

  • role of Hepatocyte Nuclear Factors in growth hormone regulated sexually dimorphic expression of liver cytochromes p450
    Growth Factors Journal, 2004
    Co-Authors: Christopher A Wiwi, David J Waxman
    Abstract:

    The liver is a sexually dimorphic organ in many species, including humans. In rodent models, dramatic sex differences characterize the expression of numerous plasma proteins, receptors and other signaling molecules, and enzymes of steroid and foreign compound metabolism, including members of the cytochrome P450 (CYP) superfamily. The sexual dimorphism of liver gene expression is dictated by the temporal pattern of plasma growth hormone (GH) stimulation, which is intermittent and highly pulsatile in males and more frequent in females. Many liver-specific genes, including CYP genes, are regulated by the coordinated action of multiple hepatic Nuclear Factors (HNFs) through a complex transcriptional hierarchy. These HNFs are proposed to collaborate with the GH pulse-activated latent cytoplasmic transcription factor STAT5b to regulate the sex-dependent expression of liver CYPs. This hypothesis is supported by the finding that certain HNFs are regulated by GH and exhibit a differential responsiveness to the sex...

  • synergistic action of Hepatocyte Nuclear Factors 3 and 6 oncyp2c12 gene expression and suppression by growth hormone activated stat5b proposed model for female specific expression ofcyp2c12 in adult rat liver
    Journal of Biological Chemistry, 2000
    Co-Authors: Nathalie Delesquetouchard, Soohee Park, David J Waxman
    Abstract:

    Growth hormone (GH) exerts sexually dimorphic effects on liver gene transcription through its sex-dependent temporal pattern of pituitary hormone secretion. CYP2C12 encodes a female-specific rat liver P450 steroid hydroxylase whose expression is activated by continuous GH stimulation of Hepatocytes. Presently, we investigated the role of liver-enriched and GH-regulated transcription Factors in the activation of CYP2C12 gene expression in GH-stimulated liver cells. Transcription of a CYP2C12 promoter-luciferase reporter gene in transfected HepG2 cells was activated 15–40-fold by the liver-enriched Hepatocyte Nuclear factor (HNF) 3α, HNF3β, and HNF6. Synergistic interactions leading to an ∼300-fold activation of the promoter by HNF3β in combination with HNF6 were observed. 5′-Deletion analysis localized the HNF6 response to a single 5′-proximal 96-nucleotide segment. By contrast, the stimulatory effects of HNF3α and HNF3β were attributable to five distinct regions within the 1.6-kilobase CYP2C12 proximal promoter. GH activation of the signal transducer and transcriptional activator STAT5b, which proceeds efficiently in male but not female rat liver, inhibited CYP2C12 promoter activation by HNF3β and HNF6, despite the absence of a classical STAT5-binding site. The female-specific pattern of CYP2C12 expression is thus proposed to reflect the positive synergistic action in female liver of liver-enriched and GH-regulated transcription Factors, such as HNF3β and HNF6, coupled with a dominant inhibitory effect of GH-activated STAT5b that is manifest in males.