THE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR ALPHA-2 SUBUNIT GENE PROMOTER IS ACTIVATED BY THE BRN-3B POU FAMILY TRANSCRIPTION FACTOR AND NOT BY BRN-3A OR BRN-3C

The regulatory region of the neuronal nicotinic acetylcholine receptor alpha 2 subunit gene, which contains six copies of the octamer-relate d sequence CCCCATGCAAT, is activated by the Brn-3b POU family transcri ption factor but not by the closely related factors Brn-3a and Brn-3c. This effect is in contrast to the previously documented inhibitory ef fect of Brn-3b on octamer-containing promoters that are activated by B rn-3a and Brn-3c. Activation of the alpha 2 gene by Brn-3b requires th at both the POU domain and other N-terminal sequences are derived from Brn-3b and is dependent on the intactness of the alpha 2 gene regulat ory region, being lost in truncated derivatives containing one, two, o r four copies of the octamer-related sequence. Surprisingly, however, these truncated derivatives are activated by Brn-3c. These effects are discussed in terms of both the influence of the target sequence and i ts context in the promoter on activation by the various forms of Brn-3 as well as of the processes that restrict expression of the alpha 2 s ubunit gene to a few cells in the nervous system.