The levels of the antagonistic POU family transcription factors Brn-3a and Brn-3b in neuronal cells are regulated in opposite directions by serum growth factors

Abstract

The Brn-3a and Brn-3b proteins are closely related POU family transcription factors with generally antagonistic effects on gene expression. We show that transfer of ND7 neuronal cells to medium containing either no foetal calf serum or low concentrations of serum results in a rise in Brn-3a mRNA levels and a fall in Brn-3b mRNA levels, although the precise serum dependence of these two effects differ. These effects can be reversed by addition of specific growth factors to the medium lacking serum, although not all growth factor treatments which suppress the rise in Brn-3a can reverse the fall in Brn-3b levels. These effects do not correlate with the effects of each treatment on cellular proliferation indicating that they are not simply a consequence of changes in proliferation. Interestingly however, treatments which produce a rise in Brn-3a levels also induce the outgrowth of neuritic processes. Hence the expression of a functionally antagonistic pair of POU factors is regulated in opposite directions by treatments with serum growth factors and this is likely to represent one means by which such growth factors modulate the gene expression patterns and ultimately the behaviour of neuronal cells.