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[PMID]:29233692
[Au] Autor:Tsukamoto D; Ito M; Takamatsu N
[Ad] Endereço:Laboratory of Molecular Biology, Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Minamiku, Sagamihara, 252-0373, Japan. Electronic address: tsukamot@kitasato-u.ac.jp.
[Ti] Título:Epigenetic regulation of hibernation-associated HP-20 and HP-27 gene transcription in chipmunk liver.
[So] Source:Biochem Biophys Res Commun;495(2):1758-1765, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The chipmunk hibernation-related proteins (HPs) HP-20 and HP-27 are components of a 140-kDa complex that dramatically decreases in the blood during hibernation. The HP-20 and HP-27 genes are expressed specifically in the liver and are downregulated in hibernating chipmunks. Hibernation-associated physiological changes are assumed to be under genetic control. Therefore, to elucidate the molecular mechanisms of hibernation, here we examined the mechanisms behind the altered HP-20 and HP-27 gene expression in nonhibernating versus hibernating chipmunks. Chromatin immunoprecipitation (ChIP) analyses revealed that histone H3 on the HP-20 and HP-27 gene promoters was highly acetylated at lysine (K) 9 and K14 and highly trimethylated at K4 in the liver of nonhibernating chipmunks, while these active histone modifications were nearly absent in hibernating chipmunks. Furthermore, histone acetyltransferases and a histone methyltransferase were associated with the HP-20 and HP-27 gene promoters primarily in nonhibernating chipmunks. Consistent with a previous finding that HNF-1 and USF can activate HP-20 and HP-27 gene transcription by binding to the proximal promoter region, ChIP-quantitative PCR (qPCR) analyses revealed that significantly less HNF-1 and USF were bound to these gene promoters in hibernating than in nonhibernating chipmunks. These findings collectively indicated that the hibernation-associated HP-20 and HP-27 gene expression is epigenetically regulated at the transcriptional level by the binding of HNF-1 and USF to their proximal promoters, and that histone modification has a key role in hibernation-associated transcriptional regulation.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/genética
Proteínas Sanguíneas/fisiologia
Hibernação/genética
Hibernação/fisiologia
Sciuridae/genética
Sciuridae/fisiologia
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Epigênese Genética
Expressão Gênica
Fator 1 Nuclear de Hepatócito/metabolismo
Histonas/metabolismo
Masculino
Regiões Promotoras Genéticas
Ligação Proteica
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Transcrição Genética
Fatores Estimuladores Upstream/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Proteins); 0 (HP-20 protein, Tamias asiaticus); 0 (HP-27 protein, Tamias asiaticus); 0 (Histones); 0 (RNA, Messenger); 0 (Upstream Stimulatory Factors); 126548-29-6 (Hepatocyte Nuclear Factor 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE


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[PMID]:28204827
[Au] Autor:Dong B; Singh AB; Shende VR; Liu J
[Ad] Endereço:Department of Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA 94304, USA.
[Ti] Título:Hepatic HNF1 transcription factors control the induction of PCSK9 mediated by rosuvastatin in normolipidemic hamsters.
[So] Source:Int J Mol Med;39(3):749-756, 2017 Mar.
[Is] ISSN:1791-244X
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Proprotein convertase subtilisin/kexin type 9 (PCSK9) impedes low­density lipoprotein (LDL) receptor (LDLR)-mediated LDL-cholesterol uptake and has hence emerged as a critical regulator of serum cholesterol levels and a new therapeutic target for the treatment of hypercholesterolemia. Statins have been shown to elevate circulating PCSK9 levels by stimulating PCSK9 gene transcription, which reduces the clinical efficacy of statin in LDL­cholesterol reduction. The transcription of PCSK9 is partially controlled by the hepatocyte nuclear factor 1 (HNF1) binding site embedded in the proximal region of its promoter. In this study, we utilized adenoviral shRNA delivery vectors to generate liver-specific knockdown of HNF1α (Ad­shHNF1α) or HNF1ß (Ad­shHNF1ß) in hamsters to examine the impact of reduced hepatic expression of HNF1 transcription factors on statin­induced elevation of PCSK9 expression and serum cholesterol levels. We showed that the administration of rosuvastatin (RSV) to normolipidemic hamsters significantly augmented hepatic PCSK9 expression and serum PCSK9 levels. In addition, RSV treatment increased hepatic HNF1α protein levels without a clear effect on HNF1α mRNA expression. Injection of Ad-shHNF1α or Ad­shHNF1ß into hamsters both blunted RSV­induced elevation of PCSK9 serum concentration and hepatic mRNA and protein levels, which led to significant increases in liver LDLR protein abundance. Furthermore, hepatic depletion of HNF1 factors lowered circulating total cholesterol and non­high density lipoprotein cholesterol levels in RSV­treated hamsters. Our study demonstrates that both HNF1α and HNF1ß are positive regulators of hepatic PCSK9 transcription in hamster species and that transient, liver-specific knockdown of either HNF1α or HNF1ß could antagonize the RSV­induced elevation of serum PCSK9 and reduce circulating cholesterol levels.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/efeitos dos fármacos
Fator 1 Nuclear de Hepatócito/metabolismo
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia
Pró-Proteína Convertase 9/genética
Rosuvastatina Cálcica/farmacologia
[Mh] Termos MeSH secundário: Adenoviridae/genética
Animais
Sequência de Bases
Colesterol/sangue
Clonagem Molecular
Cricetinae
Técnicas de Silenciamento de Genes
Inativação Gênica
Vetores Genéticos/genética
Fator 1 Nuclear de Hepatócito/genética
Fator 1-alfa Nuclear de Hepatócito/genética
Fator 1-alfa Nuclear de Hepatócito/metabolismo
Fator 1-beta Nuclear de Hepatócito/genética
Fator 1-beta Nuclear de Hepatócito/metabolismo
Fígado/metabolismo
Masculino
Pró-Proteína Convertase 9/sangue
Pró-Proteína Convertase 9/metabolismo
RNA Interferente Pequeno/genética
Receptores de LDL/metabolismo
Transdução de Sinais
Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo
Transdução Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hepatocyte Nuclear Factor 1-alpha); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (RNA, Small Interfering); 0 (Receptors, LDL); 0 (Sterol Regulatory Element Binding Proteins); 126548-29-6 (Hepatocyte Nuclear Factor 1); 138674-15-4 (Hepatocyte Nuclear Factor 1-beta); 83MVU38M7Q (Rosuvastatin Calcium); 97C5T2UQ7J (Cholesterol); EC 3.4.21.- (Proprotein Convertase 9)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170315
[Lr] Data última revisão:
170315
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.3892/ijmm.2017.2879


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[PMID]:27844479
[Au] Autor:Chen Y; Yu Q; Huang Z; Wang B; Xu Q; Lan L; Chang G; Zhang Y; Chen G
[Ad] Endereço:a The Key Laboratory of Animal Genetics & Breeding and Molecular Design of Jiangsu Province , Yangzhou University , Yangzhou , P.R. China.
[Ti] Título:Specific expression and promoter analysis of the albumin gene promoter of the duck (Anas platyrhynchos domesticus).
[So] Source:Br Poult Sci;58(1):19-25, 2017 Feb.
[Is] ISSN:1466-1799
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:1. Albumin (ALB) is a serum protein most highly expressed in liver and regarded as an effective indicator for liver pathologies. The objectives of this study were to determine the expression of duck ALB gene (duALB) in various non-hepatic tissues and identify the potential cis-regulatory elements in the promoter. 2. A model was established to assess duALB promoter activity in different cell lines by construction of a duALB promoter-driven GFP (Green Fluorescent Protein)-expressing vector, which exhibited high expression activity in liver-derived cells and lower expression in other cells. Through the firefly luciferase reporter gene driven by a series of constructs carrying progressive deletions, the core transcriptional regulatory region within the duALB promoter was identified. Mutations in candidate-binding sites were made by site-directed mutagenesis. 3. The core transcriptional regulatory region was located in the -190/-51 bp region. This region contains three potential transcription factor-binding sites, one each for hepatocyte nuclear factor (HNF-3ß) (-158/-149), CCAAT/Enhancer-binding protein element (C/EBPα) (-119/-107) and nuclear factor-1 (HNF-1) (-67/-57). Site-directed mutagenesis of HNF-1 and C/EBPα-binding sites resulted in a significant reduction in duALB promoter activity. Two potential cis-regulatory elements (C/EBPα and HNF-1) were responsible for its transcriptional activity in liver-derived cells. 4. These findings contribute to the further understanding of the fundamental mechanisms of ALB gene regulation and the use of tissue-specific gene promoters to regulate tissue-specific expression of exogenous genes in vivo.
[Mh] Termos MeSH primário: Patos/genética
Expressão Gênica/genética
Regiões Promotoras Genéticas/genética
Albumina Sérica/genética
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação/genética
Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo
DNA/metabolismo
Regulação da Expressão Gênica/genética
Vetores Genéticos
Proteínas de Fluorescência Verde/genética
Fator 1 Nuclear de Hepatócito/metabolismo
Fator 3-beta Nuclear de Hepatócito/metabolismo
Fígado/metabolismo
Mutagênese Sítio-Dirigida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCAAT-Enhancer-Binding Protein-alpha); 0 (Serum Albumin); 126548-29-6 (Hepatocyte Nuclear Factor 1); 135845-92-0 (Hepatocyte Nuclear Factor 3-beta); 147336-22-9 (Green Fluorescent Proteins); 9007-49-2 (DNA)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170213
[Lr] Data última revisão:
170213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161116
[St] Status:MEDLINE
[do] DOI:10.1080/00071668.2016.1236361


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[PMID]:26337491
[Au] Autor:Grabmaier U; Rottstegge I; Offers M; Ziegler T; Brenner C; Huber BC; Seissler J
[Ad] Endereço:IV Medical Department, Ludwig Maximilians University, Munich, Germany - ulrich.grabmaier@med.uni-muenchen.de.
[Ti] Título:Isolation and expansion of cytokeratin positive progenitor cells from adult murine pancreatic ducts expressing Pdx-1, Nestin, Sox9, MafA and hepatic nuclear factors.
[So] Source:Minerva Endocrinol;42(1):30-40, 2017 Mar.
[Is] ISSN:1827-1634
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Recent studies suggest that stem cells may represent a putative source for the generation of beta cells. However, the identity and characteristics of stem cells from adult pancreas and conditions for their large scale expansion are still poorly defined. METHODS: DPC were isolated from adult pancreatic ducts of C57Bl/6 mice. Expression profile was investigated by PCR, FACS and immunohistochemistry. RESULTS: DPC express a panel of stem cell associated markers such as Pdx-1, cytokeratin-19 (CK19), nestin, Sox9 together with the transcription factor MafA and hepatic nuclear factors HNF1ß, HNF3ß, HNF4α und HNF6. This gene expression profile is suggesting that DPC might be a promising tool for endocrine differentiation. After stimulation with picolinic acid and hypoxia, DPC expressed the endocrine differentiation marker Ngn3. Nevertheless, insulin production was not observed. CONCLUSIONS: We here describe a protocol for the isolation end expansion of murine pancreatic ductal progenitor cells (DPC) displaying high self-renewal, spheroid- and colony-forming capacity. Further studies are required to elucidate the conditions for differentiation into mature pancreatic endocrine cell lineages.
[Mh] Termos MeSH primário: Fator 1 Nuclear de Hepatócito/genética
Proteínas de Homeodomínio/genética
Queratinas/metabolismo
Fatores de Transcrição Maf Maior/genética
Nestina/genética
Ductos Pancreáticos/citologia
Ductos Pancreáticos/metabolismo
Fatores de Transcrição SOX9/genética
Células-Tronco/metabolismo
Transativadores/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Linhagem da Célula
Camundongos
Camundongos Endogâmicos BALB C
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Homeodomain Proteins); 0 (Maf Transcription Factors, Large); 0 (Mafa protein, mouse); 0 (Nes protein, mouse); 0 (Nestin); 0 (SOX9 Transcription Factor); 0 (Sox9 protein, mouse); 0 (Trans-Activators); 0 (pancreatic and duodenal homeobox 1 protein); 126548-29-6 (Hepatocyte Nuclear Factor 1); 68238-35-7 (Keratins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150905
[St] Status:MEDLINE
[do] DOI:10.23736/S0391-1977.16.02351-8


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[PMID]:26808453
[Au] Autor:Browne JA; Yang R; Eggener SE; Leir SH; Harris A
[Ad] Endereço:Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL, USA.
[Ti] Título:HNF1 regulates critical processes in the human epididymis epithelium.
[So] Source:Mol Cell Endocrinol;425:94-102, 2016 Apr 15.
[Is] ISSN:1872-8057
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:The luminal environment of the epididymis participates in sperm maturation and impacts male fertility. It is dependent on the coordinated expression of many genes encoding proteins with a role in epithelial transport. We identified cis-regulatory elements for critical genes in epididymis function, by mapping open chromatin genome-wide in human epididymis epithelial (HEE) cells. Bioinformatic predictions of transcription factors binding to the regulatory elements suggested an important role for hepatocyte nuclear factor 1 (HNF1) in the transcriptional program of these cells. Chromatin immunoprecipitation and deep sequencing (ChIP-seq) revealed HNF1 target genes in HEE cells. In parallel, the contribution of HNF1 to the transcriptome of HEE cells was determined by RNA-seq, following siRNA-mediated depletion of both HNF1α and HNF1ß transcription factors. Repression of these factors caused differential expression of 1892 transcripts (902 were downregulated and 990 upregulated) in comparison to non-targeting siRNAs. Differentially expressed genes with HNF1 ChIP-seq peaks within 20 kb were subject to gene ontology process enrichment analysis. Among the most significant processes associated with down-regulated genes were epithelial transport of water, phosphate and bicarbonate, all critical processes in epididymis epithelial function. Measurements of intracellular pH (pHi) confirmed a role for HNF1 in regulating the epididymis luminal environment.
[Mh] Termos MeSH primário: Epididimo/metabolismo
Redes Reguladoras de Genes
Fator 1 Nuclear de Hepatócito/genética
Fator 1 Nuclear de Hepatócito/metabolismo
Elementos Reguladores de Transcrição
[Mh] Termos MeSH secundário: Células Cultivadas
Imunoprecipitação da Cromatina
Biologia Computacional/métodos
Epididimo/citologia
Regulação da Expressão Gênica
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Masculino
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
126548-29-6 (Hepatocyte Nuclear Factor 1)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170415
[Lr] Data última revisão:
170415
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160126
[St] Status:MEDLINE


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[PMID]:26427720
[Au] Autor:Rondini EA; Pant A; Kocarek TA
[Ad] Endereço:Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan.
[Ti] Título:Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Intermediates of the Cholesterol Biosynthetic Pathway in Primary Cultured Rat Hepatocytes.
[So] Source:J Pharmacol Exp Ther;355(3):429-41, 2015 Dec.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytosolic sulfotransferase 1C2 (SULT1C2) is expressed in the kidney, stomach, and liver of rats; however, the mechanisms regulating expression of this enzyme are not known. We evaluated transcriptional regulation of SULT1C2 by mevalonate (MVA)-derived intermediates in primary cultured rat hepatocytes using several cholesterol synthesis inhibitors. Blocking production of mevalonate with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin (30 µM), reduced SULT1C2 mRNA content by ∼40% whereas the squalene synthase inhibitor squalestatin (SQ1, 0.1 µM), which causes accumulation of nonsterol isoprenoids, increased mRNA content by 4-fold. Treatment with MVA (10 mM) strongly induced SULT1C2 mRNA by 12-fold, and this effect was blocked by inhibiting squalene epoxidase but not by more distal cholesterol inhibitors, indicating the effects of MVA are mediated by postsqualene metabolites. Using rapid amplification of cDNA ends (RACE), we characterized the 5' end of SULT1C2 mRNA and used this information to generate constructs for promoter analysis. SQ1 and MVA increased reporter activity by ∼1.6- and 3-fold, respectively, from a construct beginning 49 base pairs (bp) upstream from the longest 5'-RACE product (-3140:-49). Sequence deletions from this construct revealed a hepatocyte nuclear factor 1 (HNF1) element (-2558), and mutation of this element reduced basal (75%) and MVA-induced (30%) reporter activity and attenuated promoter activation following overexpression of HNF1α or 1ß. However, the effects of SQ1 were localized to a more proximal promoter region (-281:-49). Collectively, our findings demonstrate that cholesterol biosynthetic intermediates influence SULT1C2 expression in rat primary hepatocytes. Further, HNF1 appears to play an important role in mediating basal and MVA-induced SULT1C2 transcription.
[Mh] Termos MeSH primário: Colesterol/biossíntese
Regulação Enzimológica da Expressão Gênica/fisiologia
Hepatócitos/enzimologia
Sulfotransferases/biossíntese
Sulfotransferases/genética
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Genes Reporter
Fator 1 Nuclear de Hepatócito/genética
Fator 1 Nuclear de Hepatócito/metabolismo
Hepatócitos/efeitos dos fármacos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia
Masculino
Ácido Mevalônico/farmacologia
Cultura Primária de Células
RNA Mensageiro/biossíntese
Ratos
Ratos Sprague-Dawley
Esqualeno Mono-Oxigenase/antagonistas & inibidores
Sulfotransferases/efeitos dos fármacos
Transfecção
Ácidos Tricarboxílicos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (RNA, Messenger); 0 (Tricarboxylic Acids); 1117HVX02L (squalestatin 1); 126548-29-6 (Hepatocyte Nuclear Factor 1); 97C5T2UQ7J (Cholesterol); EC 1.14.14.17 (Squalene Monooxygenase); EC 2.8.2.- (Sulfotransferases); EC 2.8.2.- (Sult1c2 protein, rat); S5UOB36OCZ (Mevalonic Acid)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151003
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.115.226365


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[PMID]:25989892
[Au] Autor:Gamou T; Habano W; Terashima J; Ozawa S
[Ad] Endereço:Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan.
[Ti] Título:A CAR-responsive enhancer element locating approximately 31 kb upstream in the 5'-flanking region of rat cytochrome P450 (CYP) 3A1 gene.
[So] Source:Drug Metab Pharmacokinet;30(2):188-97, 2015 Apr.
[Is] ISSN:1880-0920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Constitutive androstane receptor (CAR) is one of the principal regulators of hepatic cytochrome P450s (CYPs) 3A (CYP3A). cDNA-mediated expression of a mature rat CAR (rCAR) into rat hepatoma cells induced CYP3A1 and CYP2B mRNAs. Aberrant rCAR failed in these inductions. Three important human CYP3A4 regulatory elements (REs), proximal ER6 (proER6), xenobiotic responsive enhancer module (XREM) and constitutive liver enhancer module (CLEM), support constitutive and inducible expression of CYP3As mediated by CAR and pregnane X receptor (PXR). NHR-scan software predicted proER6, XREM and CLEM at -255 b, -8 kb and -11.5 kb, respectively of CYP3A4, but neither XREM nor CLEM was predicted in rat CYP3A. A luciferase reporter construct carrying a 5'-flanking sequence of CYP3A1 (-31,739 to -31,585 from its transcription initiation site) revealed important for the rCAR-dependent transactivation of CYP3A1. This region includes two putative binding motifs of nuclear receptors (DR4 and DR2), a putative hepatocyte nuclear factor-1 binding motif (HNF1), nuclear factor-kappa B binding motif (NFκB), activator protein 1 binding motif (AP-1), and ecotropic viral integration site 1 binding motif (Evi1). We hereby conclude DR4 and/or DR2 motifs being primarily responsible and HNF1 being synergistically functioning elements for the rCAR-mediated transcription of CYP3A1.
[Mh] Termos MeSH primário: Região 5´-Flanqueadora
Citocromo P-450 CYP3A/genética
Hepatócitos/enzimologia
Receptores Citoplasmáticos e Nucleares/genética
Elementos de Resposta
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Carcinoma Hepatocelular/enzimologia
Carcinoma Hepatocelular/genética
Linhagem Celular Tumoral
Citocromo P-450 CYP3A/metabolismo
Dexametasona/farmacologia
Regulação Enzimológica da Expressão Gênica
Genes Reporter
Fator 1 Nuclear de Hepatócito/metabolismo
Hepatócitos/efeitos dos fármacos
Neoplasias Hepáticas/enzimologia
Neoplasias Hepáticas/genética
Masculino
Ligação Proteica
RNA Mensageiro/metabolismo
Ratos Endogâmicos F344
Receptores Citoplasmáticos e Nucleares/metabolismo
Transcrição Genética
Ativação Transcricional
Transfecção
Ácidos Tricarboxílicos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Tricarboxylic Acids); 0 (constitutive androstane receptor); 126548-29-6 (Hepatocyte Nuclear Factor 1); 7S5I7G3JQL (Dexamethasone); EC 1.14.14.1 (Cyp3a1 protein, rat); EC 1.14.14.1 (Cytochrome P-450 CYP3A)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:150520
[Lr] Data última revisão:
150520
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150521
[St] Status:MEDLINE


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[PMID]:24905847
[Au] Autor:Horikawa Y; Enya M; Fushimi N; Fushimi Y; Takeda J
[Ad] Endereço:Department of Diabetes and Endocrinology, Gifu University, Graduate School of Medicine, Gifu, Japan.
[Ti] Título:Screening of diabetes of youth for hepatocyte nuclear factor 1 mutations: clinical phenotype of HNF1ß-related maturity-onset diabetes of the young and HNF1α-related maturity-onset diabetes of the young in Japanese.
[So] Source:Diabet Med;31(6):721-7, 2014 Jun.
[Is] ISSN:1464-5491
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: To compare the prevalence and clinical features of HNF1ß-related MODY and HNF1α-related MODY in Japanese. METHODS: We enrolled 230 Japanese patients with suspected MODY and examined them for HNF1α and HNF1ß mutations. We characterized the clinical features of HNF1ß-related MODY (HNF1ß-MODY) and HNF1α-related MODY (HNF1α-MODY). RESULTS: Six patients had HNF1ß mutations, four of which were large gene deletions and 24 patients had HNF1α mutations, which included one gene deletion. The mean fasting plasma glucose level at onset of HNF1ß-MODY was considerably higher and the age of onset of HNF1ß-MODY was considerably older than they were for HNF1α-MODY, while the mean BMI and C-peptide index at onset were similar. Three patients with HNF1ß-MODY were found to have dorsal pancreatic agenesis and four of them had whole-gene deletion. Five of the patients with HNF1ß-MODY had insulin secretion defects and were treated with insulin, and four of these did not have a parent with overt diabetes. CONCLUSION: HNF1ß-MODY may present as ß-cell dysfunction in Japanese rather than as hyperinsulinaemia, which it does among European/American. This dysfunction might result from an intrinsically lower capacity for insulin secretion in Japanese. HNF1ß-MODY has an older age of onset than HNF1α-MODY, which may suggest lower penetrance of the disease. In addition, HNF1ß-MODY has a broad spectrum of clinical manifestations, some of which are detectable by imaging. This may be helpful in some cases for selecting HNF1ß-MODY candidates for genetic testing.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Diabetes Mellitus Tipo 2/genética
Fator 1 Nuclear de Hepatócito/genética
Mutação/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idade de Início
Análise de Variância
Criança
Feminino
Fator 1-alfa Nuclear de Hepatócito/genética
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hepatocyte Nuclear Factor 1-alpha); 126548-29-6 (Hepatocyte Nuclear Factor 1)
[Em] Mês de entrada:1502
[Cu] Atualização por classe:140609
[Lr] Data última revisão:
140609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140607
[St] Status:MEDLINE
[do] DOI:10.1111/dme.12416


  9 / 730 MEDLINE  
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[PMID]:24382740
[Au] Autor:Yamaguchi K; Huang Z; Matsumura N; Mandai M; Okamoto T; Baba T; Konishi I; Berchuck A; Murphy SK
[Ad] Endereço:Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC; Department of Gynecology and Obstetrics Graduate School of Medicine, Kyoto University, Kyoto, Japan.
[Ti] Título:Epigenetic determinants of ovarian clear cell carcinoma biology.
[So] Source:Int J Cancer;135(3):585-97, 2014 Aug 01.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Targeted approaches have revealed frequent epigenetic alterations in ovarian cancer, but the scope and relation of these changes to histologic subtype of disease is unclear. Genome-wide methylation and expression data for 14 clear cell carcinoma (CCC), 32 non-CCC and four corresponding normal cell lines were generated to determine how methylation profiles differ between cells of different histological derivations of ovarian cancer. Consensus clustering showed that CCC is epigenetically distinct. Inverse relationships between expression and methylation in CCC were identified, suggesting functional regulation by methylation, and included 22 hypomethylated (UM) genes and 276 hypermethylated (HM) genes. Categorical and pathway analyses indicated that the CCC-specific UM genes were involved in response to stress and many contain hepatocyte nuclear factor (HNF) 1-binding sites, while the CCC-specific HM genes included members of the estrogen receptor alpha (ERalpha) network and genes involved in tumor development. We independently validated the methylation status of 17 of these pathway-specific genes, and confirmed increased expression of HNF1 network genes and repression of ERalpha pathway genes in CCC cell lines and primary cancer tissues relative to non-CCC specimens. Treatment of three CCC cell lines with the demethylating agent Decitabine significantly induced expression for all five genes analyzed. Coordinate changes in pathway expression were confirmed using two primary ovarian cancer datasets (p < 0.0001 for both). Our results suggest that methylation regulates specific pathways and biological functions in CCC, with hypomethylation influencing the characteristic biology of the disease while hypermethylation contributes to the carcinogenic process.
[Mh] Termos MeSH primário: Adenocarcinoma de Células Claras/genética
Metilação de DNA
Epigenômica
Neoplasias Ovarianas/genética
[Mh] Termos MeSH secundário: Adenocarcinoma de Células Claras/patologia
Feminino
Fator 1 Nuclear de Hepatócito/genética
Fator 1 Nuclear de Hepatócito/metabolismo
Seres Humanos
Estadiamento de Neoplasias
Neoplasias Ovarianas/patologia
Reação em Cadeia da Polimerase em Tempo Real
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
126548-29-6 (Hepatocyte Nuclear Factor 1)
[Em] Mês de entrada:1407
[Cu] Atualização por classe:161025
[Lr] Data última revisão:
161025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140103
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.28701


  10 / 730 MEDLINE  
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[PMID]:23922447
[Au] Autor:O'Brien VP; Bokelmann K; Ramírez J; Jobst K; Ratain MJ; Brockmöller J; Tzvetkov MV
[Ad] Endereço:Institute of Clinical Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Germany (V.P.O., K.B., K.J., J.B., M.V.T.); and Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois (J.R., M.J.R.).
[Ti] Título:Hepatocyte nuclear factor 1 regulates the expression of the organic cation transporter 1 via binding to an evolutionary conserved region in intron 1 of the OCT1 gene.
[So] Source:J Pharmacol Exp Ther;347(1):181-92, 2013 Oct.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The organic cation transporter 1 (OCT1), also known as solute carrier family 22 member 1, is strongly and specifically expressed in the human liver. Here we show that the hepatocyte nuclear factor 1 (HNF1) regulates OCT1 transcription and contributes to the strong, liver-specific expression of OCT1. Bioinformatic analyses revealed strong conservation of HNF1 binding motifs in an evolutionary conserved region (ECR) in intron 1 of the OCT1 gene. Electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed the specific binding of HNF1 to the intron 1 ECR. In reporter gene assays performed in HepG2 cells, the intron 1 ECR increased SV40 promoter activity by 22-fold and OCT1 promoter activity by 13-fold. The increase was reversed when the HNF1 binding sites in the intron 1 ECR were mutated or the endogenous HNF1α expression was downregulated with small interfering RNA. Following HNF1α overexpression in Huh7 cells, the intron 1 ECR increased SV40 promoter activity by 11-fold and OCT1 promoter activity by 6-fold. Without HNF1α overexpression, the increases were only 3- and 2-fold, respectively. Finally, in human liver samples, high HNF1 expression was significantly correlated with high OCT1 expression (r = 0.48, P = 0.002, n = 40). In conclusion, HNF1 is a strong regulator of OCT1 expression. It remains to be determined whether genetic variants, disease conditions, or drugs that affect HNF1 activity may affect the pharmacokinetics and efficacy of OCT1-transported drugs such as morphine, tropisetron, ondansetron, tramadol, and metformin. Beyond OCT1, this study demonstrates the validity and usefulness of interspecies comparisons in the discovery of functionally relevant genomic sequences.
[Mh] Termos MeSH primário: Sequência Conservada/genética
Evolução Molecular
Fator 1 Nuclear de Hepatócito/genética
Íntrons/genética
Transportador 1 de Cátions Orgânicos/biossíntese
Transportador 1 de Cátions Orgânicos/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Animais
Bovinos
Criança
Pré-Escolar
Cães
Feminino
Regulação da Expressão Gênica
Células Hep G2
Hepatócitos/fisiologia
Seres Humanos
Macaca mulatta
Masculino
Camundongos
Meia-Idade
Pan troglodytes
Ligação Proteica/genética
Ratos
Especificidade da Espécie
Transcrição Genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Organic Cation Transporter 1); 126548-29-6 (Hepatocyte Nuclear Factor 1)
[Em] Mês de entrada:1311
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130808
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.113.206359



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