Positive and negative regulatory DNA elements including a CCArGG box are involved in the cell type-specific expression of the human muscle dystrophin gene.
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.
Gilgenkrantz
H
H
Institut Cochin de Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale U.129, Paris, France.
Hugnot
J P
JP
Lambert
M
M
Chafey
P
P
Kaplan
J C
JC
Kahn
A
A
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002872:Chromosome Deletion; D004247:DNA / Q000235:genetics; D016189:Dystrophin / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D017570:MyoD Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D015533:Transcriptional Activation; D014162:Transfection
D016189:Dystrophin; D009124:Muscle Proteins; D017570:MyoD Protein; D009687:Nuclear Proteins; D004247:DNA