Characterization of the promoter of the human KAL gene, responsible for the X-chromosome-linked Kallmann syndrome.

We report on the first characterization of the human KAL promoter (pKAL), based on the analysis of a 2-kb fragment of the 5' flanking region. As determined by primer extension, transcription of the human KAL gene is initiated at two different sites in the quail embryonic neuroretina QNR/D cell line. The promoter region is G+C rich and contains a CCAAT box, two binding sites for the SP1 transcription factor and two AP2-binding sites, but no TATA box. It also shares a motif with several neural-specific genes. The ability of four deletion mutants to drive transcription of the heterologous chloramphenicol acetyltransferase (CAT)-encoding gene was determined in transfection experiments. The mutant containing the KAL sequence from nt +2 to -435 demonstrated a tissue-specific, although weak, transcriptional activity only in the quail embryonic neuroretina K2 and QNR/D cell lines. Longer constructs did not confer any activity. Therefore, we suggest that this 437-bp segment of pKAL constitutes a neural-specific promoter which could be negatively controlled by upstream sequences.