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40
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Text
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Pages
191–197
Issue
1
Volume
272
Dublin Core
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Title
A name given to the resource
Transcriptional regulation of human oxysterol 7 alpha-hydroxylase gene (CYP7B1) by Sp1.
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
2001
2001-07
Subject
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Humans; Protein Binding; Gene Expression Regulation; Cell Line; Transfection; Base Sequence; Binding Sites/genetics; Molecular Sequence Data; Cytochrome P450 Family 7; Mutagenesis; Luciferases/genetics/metabolism; Recombinant Fusion Proteins/genetics/metabolism; CpG Islands/genetics; Cytochrome P-450 Enzyme System/*genetics/metabolism; DNA/genetics; Sequence Deletion; Sp1 Transcription Factor/metabolism/*physiology; Steroid Hydroxylases/*genetics/metabolism; Cultured; Binding; Competitive; Transcription; Genetic; Enzymologic; Tumor Cells; Site-Directed; Regulatory Sequences; Nucleic Acid/genetics
Creator
An entity primarily responsible for making the resource
Wu Z; Chiang J Y
Description
An account of the resource
Oxysterol 7 alpha-hydroxylase catalyzes hydroxylation of oxysterols and neurosterols and plays a role in the alternative bile acid synthesis pathway. This gene is widely expressed in many organs and peripheral tissues and may protect tissues from the toxicity of oxysterols. Mutation in CYP7B1 caused neonatal cholestasis. To examine the regulatory mechanisms governing CYP7B1 expression, the 5' flanking sequence of the CYP7B1 was analyzed and revealed a CpG island of about 1.2 kb. Transient transfection assays of deletion mutants of the CYP7B1 promoter-luciferase reporter gene in human liver-derived HepG2, fibroblast NT1088, and human embryonic kidney 293 cell lines revealed that the region from -291 to +189 was critical for gene transcription. Three GC box sequences located between -25 and +10 were essential for basal transcription because mutations of these sequences markedly reduced promoter activity. Sp1 and Sp3 bound to these sequences as demonstrated by DNase I footprinting assays and electrophoretic mobility shift assay. Thus, regulation of CYP7B1 transcription by Sp1 may play a pivotal role in regulating oxysterol levels, which regulate cholesterol metabolism.
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).
2001
Base Sequence
Binding
Binding Sites/genetics
Cell Line
Chiang J Y
Competitive
CpG Islands/genetics
Cultured
Cytochrome P-450 Enzyme System/*genetics/metabolism
Cytochrome P450 Family 7
Department of Integrative Medical Sciences
DNA/genetics
Enzymologic
gene
Gene Expression Regulation
Genetic
Humans
Luciferases/genetics/metabolism
Molecular Sequence Data
Mutagenesis
NEOMED College of Medicine
Nucleic Acid/genetics
Protein Binding
Recombinant Fusion Proteins/genetics/metabolism
Regulatory Sequences
Sequence Deletion
Site-Directed
Sp1 Transcription Factor/metabolism/*physiology
Steroid Hydroxylases/*genetics/metabolism
Transcription
Transfection
Tumor Cells
Wu Z