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.
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Authors | H Segev, A Honigman, H Rosen, E Leitersdorf |
Journal | Atherosclerosis
(Atherosclerosis)
Vol. 156
Issue 2
Pg. 339-47
(Jun 2001)
ISSN: 0021-9150 [Print] Ireland |
PMID | 11395030
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- RNA, Messenger
- Dexamethasone
- Cyclosporine
- Cytochrome P-450 Enzyme System
- Cholesterol
- Steroid Hydroxylases
- CYP27A1 protein, human
- Cholestanetriol 26-Monooxygenase
- Cholic Acid
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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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