Silencer-mediated repression and non-mediated activation of BDNF and c-fosgene promoters in primary glial or neuronal cells

Although the neuron-restrictive silencer element (NRSE/Regard) has been sho wn to function as a negative-acting DNA regulatory element to prevent the e xpression of neuron-specific genes in nonneuronal cells, little is known ab out its silencing effect on transcription in primary glial cells nor its ef fect on transcriptional activation in primary neurons. By DNA transfection in primary cultures of rat cortical neuronal or glial cells, we investigate d the effect of NRSE on transcription mediated by the BDNF promoter I or c- fos promoter to which NRSE sequences derived from the SCG10 gene were linke d. Transfection of plasmid DNAs to NIH3T3 fibroblasts resulted in a marked repressive effect of NRSE on BDNF promoter I- or c-fos promoter-mediated tr anscription. In primary neuronal cells, however, NRSE did not repress the b asal promoter activities of BDNF and c-fos genes and allowed the transcript ional activation of these genes induced by membrane depolarization although NRSE slightly reduced the magnitude of BDNF promoter I activation. In cont rast to neuronal cells, a marked repression of basal promoter activities of both genes was detected in primary glial culture and a two base pair-mutat ion of NRSE partially recovered the repression, These results indicate that NRSE negatively acts on its linked promoters in primary glial cells and do es not interfere an activation of linked promoters in neuronal cells. (C) 1 999 Academic Press.