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J Biol Chem, Vol. 275, Issue 12, 8895-8902, March 24, 2000
From the Wadsworth Center, New York State Department of Health and
the Department of Environmental Health and Toxicology, School of Public
Health, State University of New York at Albany, Empire State Plaza,
Albany, New York 12201-0509
CYP1A2 is a major cytochrome P-450 isoform in the
liver and the olfactory mucosa but is essentially not expressed in
other tissues. A nuclear factor 1 (NF-1) -like element was identified in the proximal promoter region of rat, mouse, rabbit, and human CYP1A2 genes through data base analysis. In
vitro DNase I footprinting with a
Identification and Functional Characterization of a Conserved,
Nuclear Factor 1-like Element in the Proximal Promoter Region of
CYP1A2 Gene Specifically Expressed in the Liver and
Olfactory Mucosa*
211 to +81 probe from the rat
CYP1A2 gene and nuclear extracts from rat liver and
olfactory mucosa revealed a single protected region corresponding to
the NF-1-like element at 129 to 111. Protein binding to this
NF-1-like element was tissue-selective and was confirmed by in
vivo footprinting in native chromatin from rat liver. Multiple
DNA-binding complexes were detected in gel-shift assays using the
CYP1A2 NF-1-like element and nuclear extracts from liver
and olfactory mucosa, all of which were supershifted in the presence of
an anti-NF1 antibody. The NF-1-like element was essential for
transcriptional activity of the CYP1A2 gene in an in
vitro transcription assay using nuclear extracts from the two
tissues. Thus, members of the NF-1 family of transcription factors may
play an important role in the tissue-selective expression of the
CYP1A2 gene in the liver and olfactory mucosa.
*
This work was supported in part by Public Health Service
Grants DC-02640 and ES-07462 from the National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Wadsworth Center, New
York State Dept. of Health, Empire State Plaza, Box 509, Albany, NY
12201-0509. Tel.: 518-486-2585; Fax: 518-486-1505; E-mail:
xding@wadsworth.org.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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