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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.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Segev H,Honigman A,Rosen H,Leitersdorf E

doi

10.1016/s0021-9150(00)00654-7

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

339-47

issue

2

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(00)00654-7

journal_volume

156

pub_type

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