Positive and negative regulatory DNA elements including a CCArGG box are involved in the cell type-specific expression of the human muscle dystrophin gene

• Published in: The Journal of biological chemistry 1992-05, Vol.267 (15), p.10823-10830
• Main Authors: Gilgenkrantz, H, Hugnot, J P, Lambert, M, Chafey, P, Kaplan, J C, Kahn, A
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Blotting, Southern; Chromosome Deletion; DNA; DNA - genetics; dystrophin; Dystrophin - genetics; gene expression; Gene Expression Regulation; Humans; man; Mice; Molecular Sequence Data; Muscle Proteins - metabolism; muscles; Muscles - metabolism; MyoD Protein; negative; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Plasmids; Polymerase Chain Reaction; positive; Promoter Regions, Genetic; promoters; Rats; regulation; regulatory; Regulatory Sequences, Nucleic Acid; Transcriptional Activation; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)50093-X

The muscle-specific promoter of the dystrophin gene is active in skeletal, cardiac, and smooth muscles and is specifically stimulated during differentiation of myoblasts into multinucleated myotubes. An 850-base pair (bp) DNA fragment upstream from the cap site is able to confer a partial muscle specificity to a reporter gene. The region between -850 and -140 bp includes nonspecific negative and positive regulatory sequences. A continuous stretch of 140 bp upstream from the cap site exhibits a striking conservation between rodents and human (93% homology) and still retains muscle preference of expression. It contains two putative binding sites for factors involved in regulation of other muscle-specific genes, a CCArGG box and an E box. This latter element, however, is unable to confer the ability to be transactivated by MyoD1 to the dystrophin promoter. The -140-bp promoter fragment exhibits antagonist effects contributed by one inhibiting sequence (nucleotide -140/-96), active in all cell types, and one activating region, from nucleotide -96 to the cap site, sufficient to confer a muscle preference of expression, in which the CCArGG box seems to play a major role.