Abstract
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.
Highlights
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
In our previous work [25] we showed that overexpression of the Brn-3a transcription factor can induce ND7 cells to extend numerous neurite processes even in full serum-containing medium, mimicking the differentiation of these cells which normally occurs when they are placed in serum-free medium
This ability of a single transcription factor to induce the complex phenotypic changes involved in neurite outgrowth is likely to depend on its ability to activate target genes whose protein products are required for this purpose
Summary
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. Unlike the situation in the nematode, three distinct Brn-3 factors have been identified in mammals that show close homology in the DNA binding POU domain but are considerably less homologous outside it and are encoded by three different genes [9, 10]. Recent experiments [8, 16] have shown that inactivation of the Brn-3b gene results in considerable loss of retinal neurons, whereas mice in which the Brn-3c gene has been inactivated show loss of olfactory neurons, and Brn-3a inactivation results in the loss of neurons in the brain stem and trigeminal ganglia [16]
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