Two E-boxes are the focal point of muscle-specific skeletal muscle type 1 Na+ channel gene expression.

The Journal of Biological Chemistry
S D KranerR L Barchi

Abstract

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 r...Continue Reading

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Citations

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Jul 16, 2008·The Journal of General Physiology·Carole HirnUrs T Ruegg
Aug 14, 1999·Nucleic Acids Research·A O Gramolini, B J Jasmin
Feb 3, 2016·Frontiers in Pharmacology·Gildas LoussouarnFlavien Charpentier
Mar 28, 2009·Journal of Neuroscience Research·Refugio García-VillegasMarco A Morales
Jul 20, 2002·The Journal of Biological Chemistry·Estela MuñozRuben Baler

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