REGULATION OF SYNAPSIN-I GENE-EXPRESSION BY THE ZINC-FINGER TRANSCRIPTION FACTOR ZIF268 EGR-1/

zif268/egr-1 is an immediate early response gene that is involved in r egulation of growth and differentiation. Its mRNA encodes a sequence-s pecific transcriptional activator containing three zinc fingers that a ct as the DNA-binding domain. Although zif268/egr-1 is expressed in th e nervous system during neuronal excitation, no target gene has yet be en identified. Here we report that the zif268/egr-1 protein bound in v itro to two sites in the proximal regulatory region of the human synap sin I gene. The zif268/egr-1 protein was also shown to stimulate trans cription from this control region in transactivation assays. Additiona lly, the presence of a putative neural-restrictive silencer element ne xt to one of the zif268/egr-1-binding sites interfered with transactiv ation in a tissue-independent manner. An analysis of the temporal expr ession pattern of zif268/egr-1 and synapsin I during neuronal differen tiation of P19 embryonal carcinoma cells revealed that zif268/egr-1 mR NA was induced on day 5 and synapsin I mRNA on day 8 after retinoic ac id treatment. From this data we conclude that the synapsin I gene is a target of the zif268 transcription factor; however, intermediate fact ors may also be involved in the activation.