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Volume 272, Number 34, Issue of August 22, 1997 pp. 21325-21333
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Coordinate Induction of the Three Neurofilament Genes by the Brn-3a Transcription Factor

(Received for publication, December 30, 1996, and in revised form, March 4, 1997)

Martin D. Smith Dagger , Peter J. Morris Dagger , Sally J. Dawson Dagger , Michael L. Schwartz § , William W. Schlaepfer § and David S. Latchman Dagger

From the Dagger  Department of Molecular Pathology, University College London Medical School, London W1P 6DB, United Kingdom and the § Division of Neuropathology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104

The POU domain transcription factor Brn-3a is able to stimulate neurite outgrowth when overexpressed in the neuronal ND7 cell line, whereas the closely related Brn-3b factor does not have this effect. We show that Brn-3a overexpression also enhances the expression of the three neurofilament genes at both the mRNA and protein levels, whereas Brn-3b overexpression has no effect. In addition Brn-3a activates the three neurofilament gene promoters in co-transfection assays in both neuronal and non-neuronal cells. As observed for enhanced neurite outgrowth, the stimulation of neurofilament gene expression and activation of the neurofilament gene promoters is observed with the isolated POU domain of Brn-3a. A single amino acid change in the POU homeodomain of Brn-3a to the equivalent amino acid in Brn-3b abolishes its ability to activate the neurofilament promoters, whereas the reciprocal change converts Brn-3b to an activator of these promoters.


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