The activity of a highly promiscuous AP-1 element can be confined to neurons by a tissue-selective repressive element.

Tissue-specific gene transcription can be determined by the use of either positive-acting or negative-acting DNA regulatory elements. We have analyzed a promoter from the growth-associated protein 43 (GAP-43) gene and found that it uses both of these mechanisms to achieve its high degree of neuron-specific activity. Two novel transcription factor binding sites, designated Cx1 and Cx2, drive promoter activity in neurons from developing cerebral cortex but not in several other cell types. The promoter also contains an activator protein 1 (AP-1) site that contributes to activity in neurons. The AP-1 site can drive promoter activity in a wide range of non-neuronal cells that express little or no endogenous GAP-43, but only in the absence of a tissue-specific repressive element located downstream of the GAP-43 TATA box. These findings suggest that the GAP-43 repressive element plays an important role in allowing AP-1 signaling pathways to modulate activity of the GAP-43 gene in neurons, without also causing inappropriate activation by AP-1 transcription factors in other cell types.