Differential regulation of neuronal nicotinic acetylcholine receptor subunit gene promoters by Brn-3 POU family transcription factors

The regulatory region of the neuronal nicotinic acetylcholine (nACh) receptor alpha 2 subunit gene is activated by the Brn-3b POU family transcription factor but not by the closely related factors Brn-3a and Brn-3c. This pattern of regulation has not previously been observed for other neuronally expressed genes, several of which, such as those encoding alpha-internexin or SNAP-25, are activated by Brn-3a and Brn-3c but repressed by Brn-3b. The alpha 3 nACh receptor subunit gene is also shown to be activated by Brn-3a but is repressed by Brn-3b and Brn-3c. In contrast, the Brn-3 POU family transcription factors have no effects on either the alpha 7 or beta 4 nACh receptor subunit genes. The actions of Brn-3b on the alpha 2 subunit are thus in contrast to the inhibitory actions of Brn-3b on several promoters that are activated by Brn-3a. The different actions of the Brn-3 POU factors on the range of nACh receptor genes tested suggests that the novel stimulation of the alpha 2 subunit by Brn-3b is specific to this subunit and not a general feature of nACh receptor genes.