Dystrophin is transcribed in brain from a distant upstream promoter.

Abstract

Dystrophin, the protein product of the Duchenne muscular dystrophy gene, is expressed in brain as well as muscle. The role of dystrophin in the brain is not clear, though one-third of Duchenne muscular dystrophy patients exhibit some degree of mental retardation. We have isolated the genomic region encoding the alternative 5' terminus of dystrophin used in the brain. Primer extension and polymerase chain reaction assays on RNA demonstrate that this region contains an alternative promoter for dystrophin used in the brain. Physical mapping of this region indicates that this brain promoter is located greater than 90 kilobases 5' to the promoter used in muscle and 400 kilobases from exon 2 to which it is spliced. The large physical distance between the promoters, taken together with their known tissue selectivities, suggests that in certain patients a deletion of either dystrophin promoter might give rise to reduced dystrophin expression selective to brain or muscle. We have identified one such individual with specific deletion of the dystrophin muscle promoter, giving rise to Becker muscular dystrophy, and we predict that specific loss of the brain promoter may be one cause of X chromosome-linked mental retardation.

Characterization of Gene Rearrangements Leading to Activation of MDR-1

“…One example where a normal tissue-specific promoter can regulate gene expression Ͼ350 kb 5Ј to the start of translation has been described for the thyroid hormone receptor ␤ gene (THRB) (33). Additional genes whose tissue-specific expression can be regulated by promoter sequences located long distances 5Ј to start of translation include CYP19 (P450 aromatase; 79 kb 5Ј) (34), HNF-4a (hepatic nuclear factor 4␣; 46 kb 5Ј) (35), and DMD (dystrophin; Ͼ90 kb 5Ј) (36). To this list we would add MDR-1 as a gene whose expression can be regulated long distance by a non-MDR-1 gene promoter.…”

Two different promoters direct expression of two distinct forms of mRNAs of human platelet‐activating factor receptor

“…Volume 322, number 2 FEBS LETTERS May 1993 mouse glucocorticoid receptor gene [22] and the human dystrophin gene [23,24]. As discussed by Schibler and Sierra [25] and Kozak [26], transcription of a single gene from multiple promoters provides additional flexibility in the control of gene expression.…”

Dystrophin Dp71 is required for neurite outgrowth in PC12 cells

“…Analysis of dystrophin gene expression has led to the identification of several Cterminal dystrophin isoforms named according to their molecular weight [9,10,15,20,31]. A 70-to 75-kDa dystrophin protein (designed Dp71) has a unique seven residues Nterminus fused to the cysteine-rich and C-terminal domains and is the most abundant dystrophin in a wide range of non-muscle tissues [5,17,28].In addition, Dp71 transcripts are alternatively spliced for exons 71-74 and 78 in several tissues; then multiple Dp71 protein products of 70-78 kDa are generated [2,3].…”