Tissue-selective Expression of alpha-Dystrobrevin is Determined by Multiple Promoters

Holzfeind, Paul J., Ambrose, Helen J., Newey, Sarah E., Nawrotzki, Ralph A., Blake, Derek J. ORCID: https://orcid.org/0000-0002-5005-4731 and Davies, Kay E. 1999. Tissue-selective Expression of alpha-Dystrobrevin is Determined by Multiple Promoters. Journal of Biological Chemistry 274 (10) , pp. 6250-6258. 10.1074/jbc.274.10.6250

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Abstract

α-Dystrobrevin, the mammalian orthologue of theTorpedo 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 α-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 α-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 α-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 α-dystrobrevin gene, has been developed to allow the regulation of this gene in different cell types and/or different developmental stages.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	24 Oct 2022 11:47
URI:	https://orca.cardiff.ac.uk/id/eprint/49315

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