Tissue-selective expression of alpha-dystrobrevin is determined by multiple promoters.
alpha-Dystrobrevin, the mammalian orthologue of the Torpedo 87-kDa postsynaptic protein, is a dystrophin-associated and dystrophin-related protein. Knockout of the gene in the mouse results in muscular dystrophy. The control of the alpha-dystrobrevin gene in the various tissues is therefore of interest. Multiple dystrobrevin isoforms differing in their domain content are generated by alternative splicing of a single gene. The data presented here demonstrate that expression of alpha-dystrobrevin from three promoters, that are active in a tissue-selective manner, also plays a role in the function of the protein in different tissues. The most proximal promoter A is active in brain and to a lesser extent in lung, whereas the most distal promoter B, which possesses several Sp1 binding sites, is restricted to brain. Promoter C, which contains multiple consensus myogenic binding sites, is up-regulated during in vitro myoblast differentiation. Interestingly, the organization and the activity of the alpha-dystrobrevin promoters is reminiscent of those in the dystrophin gene. Taken together we suggest that the multipromoter 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.
Genetics Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
P J
PJ
Holzfeind
H J
HJ
Ambrose
S E
SE
Newey
R A
RA
Nawrotzki
D J
DJ
Blake
K E
KE
Davies
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D049029:Dystrophin-Associated Proteins; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009137:Muscular Dystrophy, Animal / Q000235:genetics; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016415:Sequence Alignment
D049029:Dystrophin-Associated Proteins; D009479:Neuropeptides; C098885:dystrobrevin