Transcriptional regulation of the human alpha 5 nicotinic receptor subunitgene in neuronal and non-neuronal tissues

The human alpha 5 nicotinic receptor subunit gene appears to be expressed i n several structures of the nervous system, but also in a number of non-neu ronal tissues, with maximal expressions occurring in the entire gastrointes tinal tract, thymus and testis. To understand whether specific transcriptio nal mechanisms are involved in the tissue-specific expression of the alpha 5 subunit in neuronal and non-neuronal cells, we isolated the 5'-regulatory region of the human gene and characterized its functional properties. We d emonstrate that specific DNA elements, with positive or negative activities depending on the cell type, are responsible for the diversified expression of the alpha 5 subunit in different tissues. We therefore conclude that th e expression of the alpha 5 subunit relies on a highly complex promoter tha t uses distinct regulatory elements to comply with the different functional and developmental requirements of the various tissues and organs. (C) 2000 Published by Elsevier Science B.V. All rights reserved.