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

Citation
Pj. Holzfeind et al., Tissue-selective expression of alpha-dystrobrevin is determined by multiple promoters, J BIOL CHEM, 274(10), 1999, pp. 6250-6258
Citations number
38
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
10
Year of publication
1999
Pages
6250 - 6258
Database
ISI
SICI code
0021-9258(19990305)274:10<6250:TEOAID>2.0.ZU;2-9
Abstract
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.