Tissue-selective expression of alpha-dystrobrevin is determined by multiple promoters

alpha-Dystrobrevin, the mammalian orthologue of the Torpedo 87-kDa postsyna ptic protein, is a dystrophin-associated and dystrophin-related protein. Kn ockout of the gene in the mouse results in muscular dystrophy. The control of the alpha-dystrobrevin gene in the various tissues is therefore of inter est. Multiple dystrobrevin isoforms differing in their domain content are g enerated by alternative splicing of a single gene. The data presented here demonstrate that expression of alpha-dystrobrevin from three promoters, tha t are active in a tissue-selective manner, also plays a role in the functio n of the protein in different tissues. The most proximal promoter A is acti ve in brain and to a lesser extent in lung, whereas the most distal promote r B, which possesses several Sp1 binding sites, is restricted to brain. Pro moter C, which contains multiple consensus myogenic binding sites, is up-re gulated during in vitro myoblast differentiation. interestingly, the organi zation and the activity of the alpha-dystrobrevin promoters is reminiscent of those in the dystrophin gene. Taken together we suggest that the multipr omoter system, distributed over a region of 270 kilobases at the 5'-end of the alpha-dystrobrevin gene, has been developed to allow the regulation of this gene in different cell types and/or different developmental stages.