Transcriptional regulation of human oxysterol 7 alpha-hydroxylase gene (CYP7B1) by Sp1.

Title

Transcriptional regulation of human oxysterol 7 alpha-hydroxylase gene (CYP7B1) by Sp1.

Creator

Wu Z; Chiang J Y

Publisher

Gene

Date

2001
2001-07

Description

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.

Subject

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

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

191–197

Issue

1

Volume

272

Citation

Wu Z; Chiang J Y, “Transcriptional regulation of human oxysterol 7 alpha-hydroxylase gene (CYP7B1) by Sp1.,” NEOMED Bibliography Database, accessed April 15, 2021, https://neomed.omeka.net/items/show/5714.

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