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.
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 -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.
Zhang
J
J
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, USA.
Zhang
Q Y
QY
Guo
J
J
Zhou
Y
Y
Ding
X
X
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D017124:Conserved Sequence; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008099:Liver / Q000201:enzymology*; D051379:Mice; D051839:NFI Transcription Factors; D009687:Nuclear Proteins / Q000378:metabolism; D009831:Olfactory Mucosa / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D014018:Tissue Distribution; D014157:Transcription Factors; D015533:Transcriptional Activation; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D019388:Cytochrome P-450 CYP1A2