1
40
9
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
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n/a
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
1-11
Issue
1
Volume
41
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Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7 alpha-hydroxylase gene (CYP7A1)
Publisher
An entity responsible for making the resource available
Journal of Lipid Research
Date
A point or period of time associated with an event in the lifecycle of the resource
2000
2000-01
Subject
The topic of the resource
bile-acid synthesis; bile acids; Biochemistry & Molecular Biology; chicken ovalbumin; cholesterol metabolism; dna-binding; hepatocyte nuclear factor 4; hepatocyte nuclear factor 4; hormone-receptor superfamily; messenger-rna; orphan receptors; promoter; receptors; response elements; retinoic acid; thyroid-hormone; transcriptional regulation; upstream promoter transcription factor II
Creator
An entity primarily responsible for making the resource
Stroup D; Chiang J Y L
Description
An account of the resource
The gene for cholesterol 7 alpha-hydroxylase (CYP7A1) contains a sequence at nt -149 to -118 that was found to play a large role in determining the overall transcriptional activity and regulation of the promoter. Hepatocyte nuclear factor 4 (HNF4) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) synergistically activate transcription of the CYP7A1 promoter, Transactivation of CYP7A1 by HNF4 in the human hepatoma cell line, HepG2, was enhanced by cotransfection with COUP-TFII or the basal transcription element binding protein (BTEB), HNF4 prepared from rat liver nuclear extracts bound to oligomers homologous to the nt -146 to -134 sequences in electrophoretic mobility shift assays (EMSA), which corresponded to a conserved region containing a direct repeat of hormone response elements spaced by one nucleotide (DR1), The sequences surrounding this DR1 were found to be essential for the HNF4 transactivation. In vitro-translated COUP-TFII was found to bind the adjacent sequences from nt -139 to -128 (DRO), but COUP-TFII interacted with this region at a much lower affinity than to the COUP-TFII-site at nt -72 to -57 (DR4), Mutations at nt -139 to -128 or nt -72 to -57 reduced the COUP-TFII and HNF4 synergy; however, these COUP-TFII-binding sequences were not absolutely required for the cooperative effect of HNF4 and COUP-TFII on transactivation. These results indicated that the observed transactivation was the result of protein/protein interactions facilitated by the juxtaposition of the binding elements.
Identifier
An unambiguous reference to the resource within a given context
n/a
Format
The file format, physical medium, or dimensions of the resource
Journal Article
2000
BILE acids
bile-acid synthesis
Biochemistry & Molecular Biology
Chiang J Y L
chicken ovalbumin
cholesterol metabolism
dna-binding
Hepatocyte Nuclear Factor 4
hormone-receptor superfamily
Journal Article
Journal of lipid research
messenger-rna
orphan receptors
promoter
Receptors
Response Elements
retinoic acid
Stroup D
thyroid-hormone
transcriptional regulation
upstream promoter transcription factor II
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Pages
63–73
Issue
1
Volume
1583
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
On the mechanism of bile acid inhibition of rat sterol 12alpha-hydroxylase gene (CYP8B1) transcription: roles of alpha-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha.
Publisher
An entity responsible for making the resource available
Biochimica et biophysica acta
Date
A point or period of time associated with an event in the lifecycle of the resource
2002
2002-06
Subject
The topic of the resource
Animals; Rats; Gene Expression Regulation; Base Sequence; Cattle; Cytochrome P-450 Enzyme System/*genetics; Hepatocyte Nuclear Factor 4; *DNA-Binding Proteins; Bile Acids and Salts/*pharmacology; Steroid Hydroxylases/*genetics; alpha-Fetoproteins/genetics/*physiology; DNA; Phosphoproteins/genetics/*physiology; Steroid 12-alpha-Hydroxylase; Transcription Factors/genetics/*physiology; Sprague-Dawley; RNA; Transcription; Genetic; Promoter Regions; Messenger/genetics; Enzymologic/*drug effects/physiology; Genetic/*drug effects
Creator
An entity primarily responsible for making the resource
Yang Yizeng; Zhang Ming; Eggertsen Gosta; Chiang John Y L
Description
An account of the resource
The sterol 12alpha-hydroxylase (CYP8B1) is a key enzyme of the bile acid biosynthetic pathway. It regulates the composition of bile acids in bile, i.e. ratio between cholic acid (CA) and chenodeoxycholic acid (CDCA). In similarity with cholesterol 7alpha-hydroxylase (CYP7A1), this enzyme is subjected to a negative feedback regulation by bile acids. It has been recently reported that bile acid-activated farnesoid X receptor (FXR) induces the small heterodimer partner (SHP) that interacts with alpha-fetoprotein transcription factor (FTF) and down-regulates CYP7A1 transcription. We studied whether the same mechanism also regulated rat CYP8B1 gene transcription. Feeding rats with CDCA caused a
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*DNA-Binding Proteins
2002
alpha-Fetoproteins/genetics/*physiology
Animals
Base Sequence
Bile Acids and Salts/*pharmacology
Biochimica et biophysica acta
Cattle
Chiang John Y L
Cytochrome P-450 Enzyme System/*genetics
Department of Integrative Medical Sciences
DNA
Eggertsen Gosta
Enzymologic/*drug effects/physiology
Gene Expression Regulation
Genetic
Genetic/*drug effects
Hepatocyte Nuclear Factor 4
Messenger/genetics
NEOMED College of Medicine
Phosphoproteins/genetics/*physiology
Promoter Regions
Rats
RNA
Sprague-Dawley
Steroid 12-alpha-Hydroxylase
Steroid Hydroxylases/*genetics
Transcription
Transcription Factors/genetics/*physiology
Yang Yizeng
Zhang Ming
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Pages
1–11
Issue
1
Volume
41
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7alpha-hydroxylase gene (CYP7A1).
Publisher
An entity responsible for making the resource available
Journal of lipid research
Date
A point or period of time associated with an event in the lifecycle of the resource
2000
2000-01
Subject
The topic of the resource
Humans; Animals; Rats; Liver/metabolism; Recombinant Proteins/metabolism; Base Sequence; Mutation; DNA Primers; Cholesterol 7-alpha-Hydroxylase/*genetics; Transcription Factors/*metabolism; Hepatocyte Nuclear Factor 4; DNA-Binding Proteins/*metabolism; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Luciferases/genetics; COUP Transcription Factor II; COUP Transcription Factors; Phosphoproteins/*metabolism; Genes; Sprague-Dawley; Cultured; Genetic; Tumor Cells; Reporter; Promoter Regions; *Transcription; *Receptors; Steroid
Creator
An entity primarily responsible for making the resource
Stroup D; Chiang J Y
Description
An account of the resource
The gene for cholesterol 7alpha-hydroxylase (CYP7A1) contains a sequence at nt -149 to -118 that was found to play a large role in determining the overall transcriptional activity and regulation of the promoter. Hepatocyte nuclear factor 4 (HNF4) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) synergistically activate transcription of the CYP7A1 promoter. Transactivation of CYP7A1 by HNF4 in the human hepatoma cell line, HepG2, was enhanced by cotransfection with COUP-TFII or the basal transcription element binding protein (BTEB). HNF4 prepared from rat liver nuclear extracts bound to oligomers homologous to the nt -146 to -134 sequences in electrophoretic mobility shift assays (EMSA), which corresponded to a conserved region containing a direct repeat of hormone response elements spaced by one nucleotide (DR1). The sequences surrounding this DR1 were found to be essential for the HNF4 transactivation. In vitro-translated COUP-TFII was found to bind the adjacent sequences from nt -139 to -128 (DR0), but COUP-TFII interacted with this region at a much lower affinity than to the COUP-TFII-site at nt -72 to -57 (DR4). Mutations at nt -139 to -128 or nt -72 to -57 reduced the COUP-TFII and HNF4 synergy; however, these
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Receptors
*Transcription
2000
Animals
Base Sequence
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Chiang J Y
Cholesterol 7-alpha-Hydroxylase/*genetics
COUP Transcription Factor II
COUP Transcription Factors
Cultured
Department of Integrative Medical Sciences
DNA Primers
DNA-Binding Proteins/*metabolism
Genes
Genetic
Hepatocyte Nuclear Factor 4
Humans
Journal of lipid research
Liver/metabolism
Luciferases/genetics
Mutation
NEOMED College of Medicine
Phosphoproteins/*metabolism
Promoter Regions
Rats
Recombinant Proteins/metabolism
Reporter
Sprague-Dawley
Steroid
Stroup D
Transcription Factors/*metabolism
Tumor Cells
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Pages
514–520
Issue
4
Volume
41
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Peroxisome proliferator-activated receptor alpha (PPARalpha) and agonist inhibit cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription.
Publisher
An entity responsible for making the resource available
Journal of lipid research
Date
A point or period of time associated with an event in the lifecycle of the resource
2000
2000-04
Subject
The topic of the resource
Humans; Animals; Binding Sites; Protein Binding; Rats; Gene Expression Regulation; Species Specificity; Liver/metabolism; Transcriptional Activation; Hepatocyte Nuclear Factor 4; Response Elements; *DNA-Binding Proteins; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Retinoid X Receptors; Anticholesteremic Agents/pharmacology; Cholesterol 7-alpha-Hydroxylase/biosynthesis/*genetics; Clofibric Acid/pharmacology; Peroxisome Proliferators/pharmacology; Phosphoproteins/metabolism; Pyrimidines/pharmacology; Transcription Factors/*agonists/metabolism; Genes; Receptors; Models; Transcription; Genetic; Enzymologic; Reporter; Retinoic Acid/metabolism; Promoter Regions; Nucleic Acid; Cytoplasmic and Nuclear/*agonists; *Regulatory Sequences
Creator
An entity primarily responsible for making the resource
Marrapodi M; Chiang J Y
Description
An account of the resource
Fibrates are widely used hypolipidemic drugs that regulate the expression of many genes involved in lipid metabolism by activating the peroxisome proliferator-activated receptor alpha (PPARalpha). The objective of this study was to investigate the mechanism of action of peroxisome proliferators and PPARalpha on the transcription of cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. When cotransfected with the expression vectors for PPARalpha and RXRalpha, Wy14,643 reduced human and rat cholesterol 7alpha-hydroxylase gene (CYP7A1)/luciferase reporter activities by 88% and 43%, respectively, in HepG2 cells, but not in CV-1 or CHO cells. We have mapped the peroxisome proliferator response element (PPRE) to a conserved sequence containing the canonical AGGTCA direct repeats separated by one nucleotide (DR1). This DR1 sequence was mapped previously as a binding site for the hepatocyte nuclear factor 4 (HNF-4) which stimulates CYP7A1 transcription. Electrophoretic mobility shift assay (EMSA) showed no direct binding of in vitro synthesized PPARalpha/RXRalpha heterodimer to the DR1 sequence. PPARalpha and Wy14,643 did not affect HNF-4 binding to the DR1. However, Wy14,643 and PPARalpha/RXRalpha significantly reduced HNF-4 expression in HepG2 cells. These results suggest that PPARalpha and agonist repress cholesterol 7alpha-hydroxylase activity by reducing the availability of
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*DNA-Binding Proteins
*Regulatory Sequences
2000
Animals
Anticholesteremic Agents/pharmacology
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Binding Sites
Chiang J Y
Cholesterol 7-alpha-Hydroxylase/biosynthesis/*genetics
Clofibric Acid/pharmacology
Cytoplasmic and Nuclear/*agonists
Department of Integrative Medical Sciences
Enzymologic
Gene Expression Regulation
Genes
Genetic
Hepatocyte Nuclear Factor 4
Humans
Journal of lipid research
Liver/metabolism
Marrapodi M
Models
NEOMED College of Medicine
Nucleic Acid
Peroxisome Proliferators/pharmacology
Phosphoproteins/metabolism
Promoter Regions
Protein Binding
Pyrimidines/pharmacology
Rats
Receptors
Reporter
Response Elements
Retinoic Acid/metabolism
Retinoid X Receptors
Species Specificity
Transcription
Transcription Factors/*agonists/metabolism
Transcriptional Activation
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Pages
2192–2200
Issue
11
Volume
39
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Transcriptional activation of the cholesterol 7alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors.
Publisher
An entity responsible for making the resource available
Journal of lipid research
Date
A point or period of time associated with an event in the lifecycle of the resource
1998
1998-11
Subject
The topic of the resource
Animals; Rats; Transcription Factors/metabolism; Base Sequence; Molecular Sequence Data; DNA/metabolism; Cholesterol 7-alpha-Hydroxylase/*genetics; Hepatocyte Nuclear Factor 4; Mutagenesis; Luciferases/genetics; Retinoid X Receptors; Phosphoproteins/metabolism; COUP Transcription Factor II; COUP Transcription Factors; *Transcriptional Activation; Bile Acids and Salts/biosynthesis; DNA-Binding Proteins/metabolism; Hormones/*physiology; Oligonucleotide Probes/metabolism; Genes; Cultured; Receptors; Genetic; Cytoplasmic and Nuclear/*physiology; Tumor Cells; Reporter; Retinoic Acid/metabolism; Promoter Regions; Nucleic Acid; Site-Directed; *Receptors; Repetitive Sequences; Steroid
Creator
An entity primarily responsible for making the resource
Crestani M; Sadeghpour A; Stroup D; Galli G; Chiang J Y
Description
An account of the resource
The gene encoding cholesterol 7alpha-hydroxylase (CYP7A), the rate-limiting enzyme in bile acid synthesis, is transcriptionally regulated by bile acids and hormones. Previously, we have identified two bile acid response elements (BARE) in the promoter of the CYP7A gene. The BARE II is located in nt -149/-118 region and contains three hormone response element (HRE)-like sequences that form two overlapping nuclear receptor binding sites. One is a direct repeat separated by one nucleotide DR1 (-146- TGGACTtAGTTCA-134) and the other is a direct repeat separated by five nucleotides DR5 (-139-AGTTCAaggccGGG TAA-123). Mutagenesis of these HRE sequences resulted in lower transcriptional activity of the CYP7A promoter/reporter genes in transient transfection assay in HepG2 cells. The orphan nuclear receptor, hepatocyte nuclear factor 4 (HNF-4)1, binds to the DR1 sequence as assessed by electrophoretic mobility shift assay, and activates the CYP7A promoter/reporter activity by about 9-fold. Cotransfection of HNF-4 plasmid with another orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), synergistically activated the CYP7A transcription by 80-fold. The DR5 binds the RXR/RAR heterodimer. A hepatocyte nuclear factor-3 (HNF-3) binding site (-175-TGTTTGTTCT-166) was identified. HNF-3 was required for both basal transcriptional activity and stimulation of the rat CYP7A promoter activity by retinoic acid. Combinatorial interactions and binding of these transcription factors to BAREs may modulate the promoter activity and also mediate bile acid repression of CYP7A gene transcription.
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Receptors
*Transcriptional Activation
1998
Animals
Base Sequence
Bile Acids and Salts/biosynthesis
Chiang J Y
Cholesterol 7-alpha-Hydroxylase/*genetics
COUP Transcription Factor II
COUP Transcription Factors
Crestani M
Cultured
Cytoplasmic and Nuclear/*physiology
Department of Integrative Medical Sciences
DNA-Binding Proteins/metabolism
DNA/metabolism
Galli G
Genes
Genetic
Hepatocyte Nuclear Factor 4
Hormones/*physiology
Journal of lipid research
Luciferases/genetics
Molecular Sequence Data
Mutagenesis
NEOMED College of Medicine
Nucleic Acid
Oligonucleotide Probes/metabolism
Phosphoproteins/metabolism
Promoter Regions
Rats
Receptors
Repetitive Sequences
Reporter
Retinoic Acid/metabolism
Retinoid X Receptors
Sadeghpour A
Site-Directed
Steroid
Stroup D
Transcription Factors/metabolism
Tumor Cells
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Pages
71–82
Volume
313
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4alpha (HNF4alpha).
Publisher
An entity responsible for making the resource available
Gene
Date
A point or period of time associated with an event in the lifecycle of the resource
2003
2003-08
Subject
The topic of the resource
Humans; Cell Line; Transfection; Gene Expression Regulation/drug effects; Base Sequence; Binding Sites/genetics; Response Elements/genetics; Molecular Sequence Data; Mutation; Chenodeoxycholic Acid/pharmacology; Transcription Factors/genetics/*metabolism; Hepatocyte Nuclear Factor 4; Mutagenesis; *DNA-Binding Proteins; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Bile Acids and Salts/*pharmacology; Cholestanetriol 26-Monooxygenase; DNA/chemistry/genetics; Luciferases/genetics/metabolism; Phosphoproteins/genetics/*metabolism; Recombinant Fusion Proteins/genetics/metabolism; Steroid Hydroxylases/*genetics; DNA; Dose-Response Relationship; Drug; Cultured; Receptors; Tumor Cells; Cloning; Molecular; Sequence Analysis; Promoter Regions; Genetic/*genetics; Cytoplasmic and Nuclear/genetics/metabolism; Site-Directed
Creator
An entity primarily responsible for making the resource
Chen Wenling; Chiang John Y L
Description
An account of the resource
Mitochondrial sterol 27-hydroxylase (CYP27A1) catalyses sterol side-chain oxidation of bile acid synthesis from cholesterol, and the first reaction of the acidic bile acid biosynthetic pathway. Hydrophobic bile acids suppress human CYP27A1 gene reporter activity when assayed in human hepatocellular blastoma HepG2 cells. Bile acids also inhibit CYP27A1 reporter activity in human embryonic kidney 293 cells. A putative bile acid response element (BARE) was mapped to a region downstream of nt -147 of the human CYP27A1 gene, within which a binding site for a liver-specific nuclear receptor, HNF4alpha, is identified. HNF4alpha strongly stimulates CYP27A1 gene transcription and mutation of its binding site markedly reduced promoter activity. Results suggest that human CYP27A1 gene transcription is suppressed by bile acids and HNF4alpha plays a pivotal role in transcriptional regulation of this gene.
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*DNA-Binding Proteins
2003
Base Sequence
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Bile Acids and Salts/*pharmacology
Binding Sites/genetics
Cell Line
Chen Wenling
Chenodeoxycholic Acid/pharmacology
Chiang John Y L
Cholestanetriol 26-Monooxygenase
Cloning
Cultured
Cytoplasmic and Nuclear/genetics/metabolism
Department of Integrative Medical Sciences
DNA
DNA/chemistry/genetics
Dose-Response Relationship
Drug
gene
Gene Expression Regulation/drug effects
Genetic/*genetics
Hepatocyte Nuclear Factor 4
Humans
Luciferases/genetics/metabolism
Molecular
Molecular Sequence Data
Mutagenesis
Mutation
NEOMED College of Medicine
Phosphoproteins/genetics/*metabolism
Promoter Regions
Receptors
Recombinant Fusion Proteins/genetics/metabolism
Response Elements/genetics
Sequence Analysis
Site-Directed
Steroid Hydroxylases/*genetics
Transcription Factors/genetics/*metabolism
Transfection
Tumor Cells
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1152/ajpgi.00258.2004" target="_blank" rel="noreferrer noopener">http://doi.org/10.1152/ajpgi.00258.2004</a>
Pages
G74–84
Issue
1
Volume
288
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7 alpha-hydroxylase gene transcription.
Publisher
An entity responsible for making the resource available
American journal of physiology. Gastrointestinal and liver physiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2005
2005-01
Subject
The topic of the resource
Bile Acids and Salts/pharmacology; Cholestasis/*physiopathology; Cholesterol 7-alpha-Hydroxylase/*biosynthesis/pharmacology; Cultured; Cytoplasmic and Nuclear/*physiology; DNA-Binding Proteins/pharmacology; Enzyme Inhibitors/*pharmacology; Genetic; Glucocorticoid; Hepatoblastoma/pathology; Hepatocyte Nuclear Factor 4; Humans; Liver Neoplasms/pathology; Messenger/analysis/biosynthesis; Phosphoproteins/pharmacology; Pregnane X Receptor; Receptors; Rifampin/*pharmacology; RNA; Steroid/*physiology; Transcription; Transcription Factors/pharmacology; Tumor Cells; Up-Regulation
Creator
An entity primarily responsible for making the resource
Li Tiangang; Chiang John Y L
Description
An account of the resource
Bile acids, steroids, and drugs activate steroid and xenobiotic receptor pregnane X receptor (PXR; NR1I2), which induces human cytochrome P4503A4 (CYP3A4) in drug metabolism and cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis in the liver. Rifampicin, a human PXR agonist, inhibits bile acid synthesis and has been used to treat cholestatic diseases. The objective of this study is to elucidate the mechanism by which PXR inhibits CYP7A1 gene transcription. The mRNA expression levels of CYP7A1 and several nuclear receptors known to regulate the CYP7A1 gene were assayed in human primary hepatocytes by quantitative real-time PCR (Q-PCR). Rifampicin reduced CYP7A1 and small heterodimer partner (SHP; NR02B) mRNA expression suggesting that SHP was not involved in PXR inhibition of CYP7A1. Rifampicin inhibited CYP7A1 reporter activity and a PXR binding site was localized to the bile acid response element-I. Mammalian two-hybrid assays revealed that PXR interacted with hepatic nuclear factor 4 alpha (HNF4 alpha, NR2A1) and rifampicin was required. Coimmunoprecipitation assay confirmed PXR interaction with HNF4 alpha. PXR also interacted with peroxisome proliferator-activated receptor gamma coactivator (PGC-1 alpha), which interacted with HNF4 alpha and induced CYP7A1 gene transcription. Rifampicin enhanced PXR interaction with HNF4 alpha and reduced PGC-1 alpha interaction with HNF4 alpha. Chromatin immunoprecipitation assay showed that PXR, HNF4 alpha, and PGC-1 alpha bound to CYP7A1 chromatin, and rifampicin dissociated PGC-1 alpha from chromatin. These results suggest that activation of PXR by rifampicin promotes PXR interaction with HNF4 alpha and blocks PGC-1 alpha activation with HNF4 alpha and results in inhibition of CYP7A1 gene transcription. Rifampicin inhibition of bile acid synthesis may be a protective mechanism against drug and bile acid-induced cholestasis.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1152/ajpgi.00258.2004" target="_blank" rel="noreferrer noopener">10.1152/ajpgi.00258.2004</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2005
American journal of physiology. Gastrointestinal and liver physiology
Bile Acids and Salts/pharmacology
Chiang John Y L
Cholestasis/*physiopathology
Cholesterol 7-alpha-Hydroxylase/*biosynthesis/pharmacology
Cultured
Cytoplasmic and Nuclear/*physiology
Department of Integrative Medical Sciences
DNA-Binding Proteins/pharmacology
Enzyme Inhibitors/*pharmacology
Genetic
Glucocorticoid
Hepatoblastoma/pathology
Hepatocyte Nuclear Factor 4
Humans
Li Tiangang
Liver Neoplasms/pathology
Messenger/analysis/biosynthesis
NEOMED College of Medicine
Phosphoproteins/pharmacology
Pregnane X Receptor
Receptors
Rifampin/*pharmacology
RNA
Steroid/*physiology
Transcription
Transcription Factors/pharmacology
Tumor Cells
Up-Regulation
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1152/ajpgi.00207.2004" target="_blank" rel="noreferrer noopener">http://doi.org/10.1152/ajpgi.00207.2004</a>
Pages
G685–695
Issue
4
Volume
288
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Cytokine regulation of human sterol 12alpha-hydroxylase (CYP8B1) gene.
Publisher
An entity responsible for making the resource available
American journal of physiology. Gastrointestinal and liver physiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2005
2005-04
Subject
The topic of the resource
Cell Line; Chenodeoxycholic Acid/pharmacology; Chromosome Mapping; DNA-Binding Proteins/genetics/metabolism; Enzyme Inhibitors/pharmacology; Gene Expression Regulation/*drug effects; Genetic/drug effects; Genetic/physiology; Hepatocyte Nuclear Factor 4; Hepatocytes/metabolism; Humans; Interleukin-1/*pharmacology; MAP Kinase Signaling System/drug effects/physiology; Messenger/antagonists & inhibitors; Mitogen-Activated Protein Kinase 8/metabolism; Mitogen-Activated Protein Kinases/antagonists & inhibitors; Phosphoproteins/genetics/metabolism; Phosphorylation; Promoter Regions; Response Elements/genetics; RNA; Steroid 12-alpha-Hydroxylase/antagonists & inhibitors/*genetics; Transcription; Transcription Factors/genetics/metabolism
Creator
An entity primarily responsible for making the resource
Jahan Asmeen; Chiang John Y L
Description
An account of the resource
Sterol 12alpha-hydroxylase (CYP8B1) catalyzes cholic acid synthesis in the liver and is feedback inhibited by bile acids. In addition to activating farnesoid X receptor (nuclear receptor subfamily 1H4), bile acids also induce inflammatory cytokines in hepatocytes. The objective of this study was to investigate the mechanism by which inflammatory cytokines inhibit human CYP8B1 gene transcription. Real-time PCR assays revealed that both chenodeoxycholic acid (CDCA) and interleukin-1beta (IL-1beta) markedly reduced CYP8B1, cholesterol 7alpha-hydroxylase CYP7A1 and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression levels in human primary hepatocytes. However, CDCA induced, but
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1152/ajpgi.00207.2004" target="_blank" rel="noreferrer noopener">10.1152/ajpgi.00207.2004</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2005
American journal of physiology. Gastrointestinal and liver physiology
Cell Line
Chenodeoxycholic Acid/pharmacology
Chiang John Y L
Chromosome Mapping
Department of Integrative Medical Sciences
DNA-Binding Proteins/genetics/metabolism
Enzyme Inhibitors/pharmacology
Gene Expression Regulation/*drug effects
Genetic/drug effects
Genetic/physiology
Hepatocyte Nuclear Factor 4
Hepatocytes/metabolism
Humans
Interleukin-1/*pharmacology
Jahan Asmeen
MAP Kinase Signaling System/drug effects/physiology
Messenger/antagonists & inhibitors
Mitogen-Activated Protein Kinase 8/metabolism
Mitogen-Activated Protein Kinases/antagonists & inhibitors
NEOMED College of Medicine
Phosphoproteins/genetics/metabolism
Phosphorylation
Promoter Regions
Response Elements/genetics
RNA
Steroid 12-alpha-Hydroxylase/antagonists & inhibitors/*genetics
Transcription
Transcription Factors/genetics/metabolism
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1074/jbc.M105117200" target="_blank" rel="noreferrer noopener">http://doi.org/10.1074/jbc.M105117200</a>
Pages
41690–41699
Issue
45
Volume
276
Dublin Core
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Title
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Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4alpha in mediating bile acid repression.
Publisher
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The Journal of biological chemistry
Date
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2001
2001-11
Subject
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*DNA-Binding Proteins; *Transcription; Base Sequence; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Bile Acids and Salts/*pharmacology; Binding Sites; Cholesterol 7-alpha-Hydroxylase/genetics; Cultured; Cytochrome P-450 Enzyme System/*genetics; Cytoplasmic and Nuclear/physiology; Genetic; Genetic/physiology; Hepatocyte Nuclear Factor 4; Humans; Molecular Sequence Data; Phosphoproteins/*physiology; Promoter Regions; Receptors; Repressor Proteins/*pharmacology; Steroid 12-alpha-Hydroxylase; Steroid Hydroxylases/*genetics; Transcription Factors/*physiology; Tumor Cells
Creator
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Zhang M; Chiang J Y
Description
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Sterol 12alpha-hydroxylase catalyzes the synthesis of cholic acid and controls the ratio of cholic acid over chenodeoxycholic acid in the bile. Transcription of CYP8B1 is inhibited by bile acids, cholesterol, and insulin. To study the mechanism of CYP8B1 transcription by bile acids, we have cloned and determined 3389 base pairs of the 5'-upstream nucleotide sequences of the human CYP8B1. Deletion analysis of CYP8B1/luciferase reporter activity in HepG2 cells revealed that the sequences from -57 to +300 were important for basal and liver-specific promoter activities. Hepatocyte nuclear factor 4alpha (HNF4alpha) strongly activated human CYP8B1 promoter activities, whereas cholesterol 7alpha-hydroxylase promoter factor (CPF), an NR5A2 family of nuclear receptors, had much less effect. Electrophoretic mobility shift assay identified an overlapping HNF4alpha- and CPF-binding site in the +198/+227 region. The human CYP8B1 promoter activities were strongly repressed by bile acids, and the bile acid response element was localized between +137 and +220. Site-directed mutagenesis of the HNF4alpha-binding site markedly reduced promoter activity and its response to bile acid repression. On the other hand, mutation of the
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1074/jbc.M105117200" target="_blank" rel="noreferrer noopener">10.1074/jbc.M105117200</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*DNA-Binding Proteins
*Transcription
2001
Base Sequence
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Bile Acids and Salts/*pharmacology
Binding Sites
Chiang J Y
Cholesterol 7-alpha-Hydroxylase/genetics
Cultured
Cytochrome P-450 Enzyme System/*genetics
Cytoplasmic and Nuclear/physiology
Department of Integrative Medical Sciences
Genetic
Genetic/physiology
Hepatocyte Nuclear Factor 4
Humans
Molecular Sequence Data
NEOMED College of Medicine
Phosphoproteins/*physiology
Promoter Regions
Receptors
Repressor Proteins/*pharmacology
Steroid 12-alpha-Hydroxylase
Steroid Hydroxylases/*genetics
The Journal of biological chemistry
Transcription Factors/*physiology
Tumor Cells
Zhang M