AUTOREGULATORY LOOP IN THE REGULATION OF THE MAMMALIAN FTZ-F1 GENE

The mammalian ftz-f1 (mftz-f1) gene encoding Ad4BP/SF-1 has been demon strated to be essential for the development of adrenal and gonadal gla nds. In a previous study, we identified an E box as the transcriptiona l element in the 5'-upstream region of the rat mftz-f1 gene. In the pr esent study, we found a steroidogenic cell-specific transcriptional el ement in the first intron of the gene. Gel mobility shift and DNase I footprint analyses clearly revealed that Ad4BP itself binds to the ele ment (Ad4 site). This finding was further supported by the positive ef fect of an Ad4BP expression vector on the transcription and by the sig nificant decrease in the transcription caused by nucleotide substituti ons within the Ad4 site. Similar loss was also caused by substitutions in the E box, indicating that the two elements are essential for the full transcriptional activity of the gene. DNase I hypersensitivity as says revealed that the chromatin structure around the Ad4 site and the E box was ''open up'' in the adrenal glands and Y-1 cells, whereas '' closed down'' in the liver. These observations indicated that the mftz -f1 gene is controlled by the autoregulatory loop in the steroidogenic tissues. The autoregulatory mechanism seems to be necessary to keep t he mftz-f1 gene activated and thus maintain the tissues differentiated .