The murine Ncx (Enx, Hox11L1) gene is specifically expressed in a neuronal subset of neural crest-derived tissues. In attempts to elucidate the regulatory DNA element of the tissue-specific expression, we sequenced the 5-flanking region of the Ncx gene. The transcriptional initiation site was determined at 297 nucleotides (؊297) upstream from the ATG start codon (؉1). A retinoic acid response element was located on the region between ؊1163 and ؊1150. Transient transfection assays with the 5-flanking sequences fused to the luciferase gene showed that the region between ؊1387 and ؊1368 was crucial for the tissue-specific enhancer activity. Furthermore, nuclear proteins extracted from neural crest-derived cells such as murine and human neuroblastoma cells bind to the DNA region between ؊1387 and ؊1368. This DNA element was also conserved in the 5-flanking region of the human NCX gene. Our observations strongly suggest that the DNA element (between ؊1387 and ؊1368) contributes to tissue-specific expression of the Ncx gene in murine and human species.

The human NCX gene, a homologue of the murine neural crest homeobox ( Ncx / Hox11L.1 ) gene whose expression is restricted to a subset of neural crest -derived tissues, was expressed in human neuroblastoma cells but not in other tumors or fibroblasts.