Muscle-specific expression of the acetylcholine receptor alpha-subunit gene requires both positive and negative interactions between myogenic factors, Sp1 and GBF factors.

AUTOR(ES)

Bessereau, J L

RESUMO

The dependence of the muscle-specific enhancer of the acetylcholine receptor alpha-subunit gene on other domains of the promoter has been analysed by performing point mutagenesis and modular reconstitution of the enhancer--promoter sequences. The enhancer is inactive in the absence of the proximal region containing an Sp1 binding site and an overlapping G-C homopolymer binding factor site (referred to as GBF). The proximal region can be replaced by an Sp1 binding site from SV40 or an MEF-2 binding site from the muscle creatine kinase gene. Specific mutation of the Sp1 site markedly affects transactivation by CMD1 or myogenin. Mutation of the GBF binding site leads to higher promoter activity in primary cultures of chick myotubes or in quail fibroblasts. In addition, binding of a purified Sp1 protein prevents the binding of GBF in vitro. It is proposed that in the case of the alpha-subunit promoter, the myogenic factors activate transcription in cooperation with Sp1, and that GBF contributes to muscle-specific expression of the promoter by interfering with Sp1 binding in nonmuscle muscle cells or myoblasts.

Documentos Relacionados

• Muscle-specific expression of the troponin I gene requires interactions between helix-loop-helix muscle regulatory factors and ubiquitous transcription factors.
• Human nicotinic acetylcholine receptor alpha-subunit isoforms: origins and expression.
• An acetylcholine receptor alpha-subunit promoter conferring preferential synaptic expression in muscle of transgenic mice.
• Induction of acetylcholine receptor alpha-subunit gene expression in chicken myotubes by blocking electrical activity requires ongoing protein synthesis.
• Both muscle-specific and ubiquitous nuclear factors are required for muscle-specific expression of the myosin heavy-chain beta gene in cultured cells.