COORDINATE INDUCTION OF THE 3 NEUROFILAMENT GENES BY THE BRN-3A TRANSCRIPTION FACTOR

The POU domain transcription factor Brn-3a is able to stimulate neurit e outgrowth when overexpressed in the neuronal ND7 cell line, whereas the closely related Brn-3b factor does not have this effect. We show t hat Brn-3a overexpression also enhances the expression of the three ne urofilament genes at both the mRNA and protein levels, whereas Brn-3b overexpression has no effect. In addition Brn-3a activates the three n eurofilament gene promoters in co-transfection assays in both neuronal and non-neuronal cells. As observed for enhanced neurite outgrowth, t he 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 Bm-Ba to the equivalent amino acid in Brn-3b abolishes its ability to activa te the neurofilament promoters, whereas the reciprocal change converts Brn-3b to an activator of these promoters.