Two E-boxes are the focal point of muscle-specific skeletal muscle type 1 Na+ channel gene expression.
We have characterized a group of cis-regulatory elements that control muscle-specific expression of the rat skeletal muscle type 1 sodium channel (SkM1) gene. These elements are located within a 3. 1-kilobase fragment that encompasses the 5'-flanking region, first exon, and part of the first intron of SkM1. We sequenced the region between -1062 and +311 and determined the start sites of transcription; multiple sites were identified between +1 and +30. The basal promoter (-65/+11) lacks cell-type specificity, while an upstream repressor (-174/-65) confers muscle-specific expression. A positive element (+49/+254) increases muscle-specific expression. Within these broad elements, two E boxes play a pivotal role. One E box at -31/-26 within the promoter, acting in part through its ability to bind the myogenic basic helix-loop-helix proteins, recruits additional factor(s) that bind elsewhere within the SkM1 sequence to control positive expression of the gene. A second E box at -90/-85 within the repressor controls negative regulation of the gene and acts through a different complex of proteins. Several of these cis-regulatory elements share both sequence and functional similarities with cis-regulatory elements of the acetylcholine receptor delta-subunit; the different arrangement of these elements may contribute to unique expression patterns for the two genes.
Kraner
S D
SD
Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA. kraner@mail.med.upenn.edu
Rich
M M
MM
Kallen
R G
RG
Barchi
R L
RL
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018983:DNA Footprinting; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D017570:MyoD Protein; C503803:Myog protein, rat; D018008:Myogenin; D015222:Sodium Channels