Neuronal and extraneuronal expression and regulation of the human alpha 5 nicotinic receptor subunit gene

The mRNA encoding the human alpha 5 nicotinic subunit was detected in sever al structures of the nervous system but appeared to be mainly expressed in cerebellum, thalamus, and the autonomic ganglia. For the first time, the al pha 5 transcript was also detected in several nonneuronal tissues, with max imal expressions being found throughout the gastrointestinal tract, thymus, and testis. Many other extraneuronal sites expressed alpha 5, but there we re also nonexpressing organs, such as the liver, spleen, and kidney. To und erstand the transcriptional mechanisms controlling such a diversified expre ssion of alpha 5 in neuronal and nonneuronal cells, we isolated the 5'-regu latory region of the human gene and characterized its properties. Here we i dentify the alpha 5 core promoter and demonstrate that the DNA regions surr ounding it contain elements (with positive or negative activities) that wor k in a tissue-specific fashion. In particular, the segment specifying the 5 '-untranslated region in neuronal cells has most of the properties of an en hancer because it activates a heterologous promoter in a position- and orie ntation-independent fashion. We therefore conclude that the expression of a lpha 5 relies on a highly complex promoter that uses distinct regulatory el ements to comply with the different functional and developmental requiremen ts of the various tissues and organs.