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 eit her positive-acting or negative-acting DNA regulatory elements. We hav e analyzed a promoter from the growth-associated protein 43 (GAP-43) g ene and found that it uses both of these mechanisms to achieve its hig h degree of neuron-specific activity. Two novel transcription factor b inding sites, designated Cx1 and Cx2, drive promoter activity in neuro ns from developing cerebral cortex but not in several other cell types . The promoter also contains an activator protein 1 (AP-1) site that c ontributes to activity in neurons. The AP-I site can drive promoter ac tivity 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 repre ssive element located downstream of the GAP-43 TATA box. These finding s suggest that the GAP-43 repressive element plays an important role i n 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.