1
40
5
-
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
17502–17507
Issue
26
Volume
269
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
Identification and characterization of a putative bile acid-responsive element in cholesterol 7 alpha-hydroxylase gene promoter.
Publisher
An entity responsible for making the resource available
The Journal of biological chemistry
Date
A point or period of time associated with an event in the lifecycle of the resource
1994
1994-07
Subject
The topic of the resource
Humans; Animals; Rats; Gene Expression Regulation; Base Sequence; Bile Acids and Salts/*metabolism; Cholesterol 7-alpha-Hydroxylase/*genetics/metabolism; Molecular Sequence Data; Recombinant Fusion Proteins/genetics/metabolism; Luciferases/genetics; DNA-Binding Proteins/metabolism; Deoxyribonuclease I; Nuclear Proteins/metabolism; Oligodeoxyribonucleotides; Thyroid Hormones/genetics; Sprague-Dawley; Genetic; Enzymologic; Cloning; Molecular; *Promoter Regions; Antigens; Polyomavirus Transforming/genetics
Creator
An entity primarily responsible for making the resource
Chiang J Y; Stroup D
Description
An account of the resource
Nucleotide sequences of a 7997-base pair SacI fragment spanning 3643 base pairs of the upstream promoter region to exon 4 of the rat cholesterol 7 alpha-hydroxylase gene (CYP7) have been determined. DNase I footprinting and electrophoretic mobility shift assay of the proximal promoter from nucleotides -346 to +36 revealed two protected regions which specifically shifted proteins in rat liver nuclear extracts. Footprint A (nucleotides -81 to -35) contained a cluster of overlapping sequence motifs of TGT3, steroid/thyroid hormone response elements (7 alpha TRE), hepatocyte nuclear factors 1 and 4, and CAAT/enhancer-binding protein alpha and has been shown to confer bile acid repression of the CYP7 gene promoter activity. Footprint B (nucleotides -148 to -129) contained a sequence motif HNF4. When footprint A (-101 to -49) or 7 alpha TRE (-73 to -55) sequence was linked upstream to a heterologous SV40 promoter/luciferase plasmid and transiently transfected into HepG2 cells, taurodeoxycholate suppressed the SV40 promoter activity. Electrophoretic mobility shift assays revealed that one or two bands shifted by the 7 alpha TRE or by a direct repeat sequence in 7 alpha TRE were absent when liver nuclear extracts of deoxycholic acid-treated rats were used. Similar gel shift patterns were also observed when human 7 alpha TRE or human liver nuclear extracts were used. The rat direct repeat sequence interacted with two polypeptides (M(r) = 57,000 and 116,000) in both rat and human liver nuclear extracts. These results suggest that hydrophobic bile acids may suppress the CYP7 gene expression by binding to a bile acid receptor which interacts with and prevents the binding of liver nuclear protein(s) to a bile acid-responsive element and that the core of bile acid-responsive element is a direct repeat.
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).
*Promoter Regions
1994
Animals
Antigens
Base Sequence
Bile Acids and Salts/*metabolism
Chiang J Y
Cholesterol 7-alpha-Hydroxylase/*genetics/metabolism
Cloning
Deoxyribonuclease I
Department of Integrative Medical Sciences
DNA-Binding Proteins/metabolism
Enzymologic
Gene Expression Regulation
Genetic
Humans
Luciferases/genetics
Molecular
Molecular Sequence Data
NEOMED College of Medicine
Nuclear Proteins/metabolism
Oligodeoxyribonucleotides
Polyomavirus Transforming/genetics
Rats
Recombinant Fusion Proteins/genetics/metabolism
Sprague-Dawley
Stroup D
The Journal of biological chemistry
Thyroid Hormones/genetics
-
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/10.1194/jlr.M002782" target="_blank" rel="noreferrer noopener">http://doi.org/10.1194/jlr.M002782</a>
Pages
832–842
Issue
4
Volume
51
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
Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.
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
2010
2010-04
Subject
The topic of the resource
*Gene Expression Regulation; Acetylation; AMP-Activated Protein Kinases/metabolism; ATP Citrate (pro-S)-Lyase/genetics/metabolism; Bile Acids and Salts/metabolism; Cells; Cholesterol 7-alpha-Hydroxylase/genetics/*metabolism; Cultured; DNA-Binding Proteins/metabolism; Enzymologic; Epigenesis; Genes; Genetic; Glucose/*administration & dosage; Hep G2 Cells; Hepatocyte Nuclear Factor 4/metabolism; Hepatocytes/*enzymology/metabolism; Histones/metabolism; Humans; Hyperglycemia/enzymology/*metabolism; Messenger/metabolism; Methylation; Reporter; RNA; RNA Interference
Creator
An entity primarily responsible for making the resource
Li Tiangang; Chanda Dipanjan; Zhang Yanqiao; Choi Hueng-Sik; Chiang John Y L
Description
An account of the resource
Bile acids play important roles in the regulation of lipid, glucose, and energy homeostasis. Recent studies suggest that glucose regulates gene transcription in the liver. The aim of this study was to investigate the potential role of glucose in regulation of bile acid synthesis in human hepatocytes. High glucose stimulated bile acid synthesis and induced mRNA expression of cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory gene in bile acid synthesis. Activation of an AMP-activated protein kinase (AMPK) decreased CYP7A1 mRNA, hepatocyte nuclear factor 4alpha (HNF4alpha) protein, and binding to CYP7A1 chromatin. Glucose increased ATP levels to inhibit AMPK and induce HNF4alpha to stimulate CYP7A1 gene transcription. Furthermore, glucose increased histone acetylation and decreased H3K9 di- and tri-methylation in the CYP7A1 chromatin. Knockdown of ATP-citrate lyase, which converts citrate to acetyl-CoA, decreased histone acetylation and attenuated glucose induction of CYP7A1 mRNA expression. These results suggest that glucose signaling also induces CYP7A1 gene transcription by epigenetic regulation of the histone acetylation status. This study uncovers a novel link between hepatic glucose metabolism and bile acid synthesis. Glucose induction of bile acid synthesis may have an important implication in metabolic control of glucose, lipid, and energy homeostasis under normal and diabetic conditions.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1194/jlr.M002782" target="_blank" rel="noreferrer noopener">10.1194/jlr.M002782</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).
*Gene Expression Regulation
2010
Acetylation
AMP-Activated Protein Kinases/metabolism
ATP Citrate (pro-S)-Lyase/genetics/metabolism
Bile Acids and Salts/metabolism
Cells
Chanda Dipanjan
Chiang John Y L
Choi Hueng-Sik
Cholesterol 7-alpha-Hydroxylase/genetics/*metabolism
Cultured
Department of Integrative Medical Sciences
DNA-Binding Proteins/metabolism
Enzymologic
Epigenesis
Genes
Genetic
Glucose/*administration & dosage
Hep G2 Cells
Hepatocyte Nuclear Factor 4/metabolism
Hepatocytes/*enzymology/metabolism
Histones/metabolism
Humans
Hyperglycemia/enzymology/*metabolism
Journal of lipid research
Li Tiangang
Messenger/metabolism
Methylation
NEOMED College of Medicine
Reporter
RNA
RNA Interference
Zhang Yanqiao
-
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.1997.273.2.G508" target="_blank" rel="noreferrer noopener">http://doi.org/10.1152/ajpgi.1997.273.2.G508</a>
Pages
G508–517
Issue
2
Volume
273
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
Identification of a bile acid response element in the cholesterol 7 alpha-hydroxylase gene CYP7A.
Publisher
An entity responsible for making the resource available
The American journal of physiology
Date
A point or period of time associated with an event in the lifecycle of the resource
1997
1997-08
Subject
The topic of the resource
Animals; Base Sequence; Bile Acids and Salts/*pharmacology; Cholesterol 7-alpha-Hydroxylase/*genetics; Cultured; DNA-Binding Proteins/metabolism; Feedback; Genes; Genes/*drug effects; Luciferases/genetics; Rats; Reporter; Tumor Cells
Creator
An entity primarily responsible for making the resource
Stroup D; Crestani M; Chiang J Y
Description
An account of the resource
The transcriptional activity of the cholesterol 7 alpha-hydroxylase gene CYP7A is repressed by bile acids. Taurine conjugates of chenodeoxycholate and deoxycholate, but not cholate and ursodeoxycholate, inhibited the CYP7A promoter/luciferase reporter activity in transient transfection assays in Hep G2 cells. A region from nucleotide (nt) -74 to -55 was found to mediate bile acid response. However, deletion of this bile acid response element (BARE-I) enhanced reporter activity but did not eliminate the bile acid response. This is due to the presence of another BARE-II located in a conserved region between nt -149 and -128. Deletion or mutations of these sequences reduced promoter activity and abolished bile acid repression. This BARE-II shares an identical AGTTCAAG core sequence with BARE-I. Electrophoretic mobility shift assays of BARE-I and BARE-II probes using Hep G2 nuclear extract and the partially purified binding activity of nt -65/-54 DNA-affinity column revealed that the same or a similar nuclear protein might bind to both BAREs. BARE-II is the major BARE involved in the transcriptional repression of the CYP7A gene by hydrophobic bile acids.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1152/ajpgi.1997.273.2.G508" target="_blank" rel="noreferrer noopener">10.1152/ajpgi.1997.273.2.G508</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).
1997
Animals
Base Sequence
Bile Acids and Salts/*pharmacology
Chiang J Y
Cholesterol 7-alpha-Hydroxylase/*genetics
Crestani M
Cultured
Department of Integrative Medical Sciences
DNA-Binding Proteins/metabolism
Feedback
Genes
Genes/*drug effects
Luciferases/genetics
NEOMED College of Medicine
Rats
Reporter
Stroup D
The American journal of physiology
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/10.1002/hep.22627" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.22627</a>
Pages
297–305
Issue
1
Volume
49
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
Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression.
Publisher
An entity responsible for making the resource available
Hepatology (Baltimore, Md.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2009
2009-01
Subject
The topic of the resource
Butadienes/pharmacology; Carcinoma; Cell Line; Chenodeoxycholic Acid/*pharmacology; Cholesterol 7-alpha-Hydroxylase/*biosynthesis; Cytoplasmic and Nuclear/metabolism/physiology; DNA-Binding Proteins/metabolism; Fibroblast Growth Factor; Fibroblast Growth Factors/drug effects/*physiology; Gene Expression/drug effects; Hepatocellular/metabolism; Hepatocytes/metabolism; Humans; Isoxazoles/pharmacology; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Nitriles/pharmacology; Receptor; Receptors; Signal Transduction/drug effects; Transcription Factors/metabolism; Tumor; Type 4/antagonists & inhibitors
Creator
An entity primarily responsible for making the resource
Song Kwang-Hoon; Li Tiangang; Owsley Erika; Strom Stephen; Chiang John Y L
Description
An account of the resource
UNLABELLED: Mouse fibroblast growth factor 15 (FGF15) and human ortholog FGF19 have been identified as the bile acid-induced intestinal factors that mediate bile acid feedback inhibition of cholesterol 7alpha-hydroxylase gene (C YP7A1) transcription in mouse liver. The mechanism underlying FGF15/FGF19 inhibition of bile acid synthesis in hepatocytes remains unclear. Chenodeoxycholic acid (CDCA) and the farnesoid X receptor (FXR)-specific agonist GW4064 strongly induced FGF19 but inhibited CYP7A1 messenger RNA (mRNA) levels in primary human hepatocytes. FGF19 strongly and rapidly repressed CYP7A1 but not small heterodimer partner (SHP) mRNA levels. Kinase inhibition and phosphorylation assays revealed that the mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) pathway played a major role in mediating FGF19 inhibition of CYP7A1. However, small interfering RNA (siRNA) knockdown of SHP did not affect FGF19 inhibition of CYP7A1. Interestingly, CDCA stimulated tyrosine phosphorylation of the FGF receptor 4 (FGFR4) in hepatocytes. FGF19 antibody and siRNA specific to FGFR4 abrogated GW4064 inhibition of CYP7A1. These results suggest that bile acid-activated FXR is able to induce FGF19 in hepatocytes to inhibit CYP7A1 by an autocrine/paracrine mechanism. CONCLUSION: The hepatic FGF19/FGFR4/Erk1/2 pathway may inhibit CYP7A1 independent of SHP. In addition to inducing FGF19 in the intestine, bile acids in hepatocytes may activate the liver FGF19/FGFR4 signaling pathway to inhibit bile acid synthesis and prevent accumulation of toxic bile acid in human livers.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/hep.22627" target="_blank" rel="noreferrer noopener">10.1002/hep.22627</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).
2009
Butadienes/pharmacology
Carcinoma
Cell Line
Chenodeoxycholic Acid/*pharmacology
Chiang John Y L
Cholesterol 7-alpha-Hydroxylase/*biosynthesis
Cytoplasmic and Nuclear/metabolism/physiology
Department of Integrative Medical Sciences
DNA-Binding Proteins/metabolism
Fibroblast Growth Factor
Fibroblast Growth Factors/drug effects/*physiology
Gene Expression/drug effects
Hepatocellular/metabolism
Hepatocytes/metabolism
Hepatology (Baltimore, Md.)
Humans
Isoxazoles/pharmacology
Li Tiangang
Mitogen-Activated Protein Kinase 1/metabolism
Mitogen-Activated Protein Kinase 3/metabolism
NEOMED College of Medicine
Nitriles/pharmacology
Owsley Erika
Receptor
Receptors
Signal Transduction/drug effects
Song Kwang-Hoon
Strom Stephen
Transcription Factors/metabolism
Tumor
Type 4/antagonists & inhibitors