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Functionally conserved xenobiotic responsive enhancer in cytochrome P450 3A7.

Abstract：

:Nuclear receptors CAR and PXR play a key role in cytochrome P450 gene induction by xenobiotics. Human cytochrome P450 3A7 (CYP3A7) is expressed from early in gestation until the perinatal period, when there is a switch in expression to CYP3A4. Here we demonstrate that a PXR and CAR responsive enhancer is located approximately 8 kb upstream of the proximal CYP3A7 promoter. This distal xenobiotic responsive enhancer module (XREM) is conserved with the XREM of CYP3A4. Interestingly, not only the XREM, but also the entire promoters exhibit 90% sequence identity up to -8.8 kb, indicating a close evolutionary distance. We propose that the promoters have coevolved to functionally conserve P450 gene induction in response to xenobiotics through CAR and PXR. Thus, nuclear receptors for xenobiotics may not only play a role to provide a survival advantage during adulthood, but also to protect the embryo against endogenous and exogenous toxins.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Bertilsson G,Berkenstam A,Blomquist P

doi

10.1006/bbrc.2000.4066

subject

Has Abstract

pub_date

2001-01-12 00:00:00

pages

139-44

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)94066-X

journal_volume

280

pub_type

杂志文章

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