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Papers In Press, published online ahead of print January 23, 2002
J. Biol. Chem, 10.1074/jbc.M111788200
Submitted on December 11, 2001
Revised on January 23, 2002
Accepted on January 23, 2002
Medical Genetics, Green Cross Institute, Seoul 135-260
Corresponding Author: myhan{at}mail.gcrl.co.kr
Dynamin I is a key molecule required for the recycling of synaptic vesicles in neurons, and it has been known that dynamin I gene expression is induced during neuronal differentiation. Our previous studies established that neuronal restriction of dynamin I gene expression is controlled by Sp1 and NE-11 element. Here, using a series of deletion constructs and site-directed mutation, we found that transcription of dynamin I gene during neuronal differentiation of N1E-115 cells is controlled primarily by the Sp1 element located between 13 to 4 bp of the dynamin I promoter. Gel shift analysis demonstrated that in addition to Sp1, Sp3 could interact with this Sp1 element. The requirement for Sp family transcription factors in dynamin I gene expression was confirmed by using the mithramycin, an inhibitor of Sp1/Sp3 binding. Mithramycin repressed dynamin I gene expression and resulted in blocking of neuronal differentiation of N1E-115 cells. The localization of the dynamin I protein was also restricted in peripheral region of nuclear by the mithramycin treatment. Thus, all of our results suggest that induction of dynamin I gene expression during N1E-115 cell differentiation is modulated by Sp1/Sp3 interactions with the dynamin I promoter and its expression is important for neuronal differentiation of the N1E-115 cells.
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