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 m ucosa 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 vitr o DNase I footprinting with a -211 to +81 probe from the rat CYP1A2 gene an d nuclear extracts from rat liver and olfactory mucosa revealed a single pr otected region corresponding to the NF-l-like element at -129 to -111, Prot ein binding to this NF-l-like element was tissue-selective and was confirme d by in vivo footprinting in native chromatin from rat liver. Multiple DNA- binding complexes were detected in gel-shift assays using the CYP1A2 NF-l-l ike element and nuclear extracts from liver and olfactory mucose, all of wh ich were supershifted in the presence of an anti-NF1 antibody, The NF-l-lik e 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 imp ortant role in the tissue-selective expression of the CYP1A2 gene in the li ver and olfactory mucosa.