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Transcriptional regulation of the human sterol 27-hydroxylase gene (CYP27) and promoter mapping.

Abstract
Recent evidence suggests that sterol 27-hydroxylase may play a role in cholesterol homeostasis and affect atherogenesis. The major objective of the study was to map and characterize the sterol 27-hydroxylase (CYP27) promoter region. Here we show that CYP27 gene has a TATA-less promoter and transcription initiates at a cluster of sites. The basic promoter is located between -166 and -187 bp from the translation initiation site. Possible positive transcription regulation sites are located at position -187 to -320 and -857 to -1087 bp. A negative transcription regulator site is located in position -320 to -413 bp. An enhancer sequence is located upstream to position -1087. CYP27 is upregulated by dexamethasone and downregulated by cyclosporin A and cholic acid. The dexamethasone responsive element is located between 1087 and 678 bp upstream to the putative ATG. Cyclosporin A affects bile acid metabolism by repressing CYP27 at the transcriptional level. The cyclosporin A- responsive element is mapped to between 1087 and 4000 bp upstream of the ATG. Cholic acid represses sterol 27-hydroxylase mRNA level by affecting the stability of its mRNA. The results obtained here imply that CYP27 has a potentially important role in cholesterol homeostasis in human cells, and is regulated by several substances that were previously shown to affect bile acid metabolism.
AuthorsH Segev, A Honigman, H Rosen, E Leitersdorf
JournalAtherosclerosis (Atherosclerosis) Vol. 156 Issue 2 Pg. 339-47 (Jun 2001) ISSN: 0021-9150 [Print] Ireland
PMID11395030 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • RNA, Messenger
  • Dexamethasone
  • Cyclosporine
  • Cytochrome P-450 Enzyme System
  • Cholesterol
  • Steroid Hydroxylases
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • Cholic Acid
Topics
  • Base Sequence
  • Cells, Cultured
  • Cholestanetriol 26-Monooxygenase
  • Cholesterol (metabolism)
  • Cholic Acid (pharmacology)
  • Chromosome Mapping
  • Cyclosporine (pharmacology)
  • Cytochrome P-450 Enzyme System (drug effects, genetics)
  • Dexamethasone (pharmacology)
  • Down-Regulation
  • Genes, Regulator
  • Hepatocytes
  • Humans
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • RNA, Messenger (analysis)
  • Sensitivity and Specificity
  • Steroid Hydroxylases (drug effects, genetics)
  • Transcription, Genetic (drug effects)
  • Transcriptional Activation (drug effects)
  • Up-Regulation

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