title: Different mechanisms regulate muscle-specific AChR gamma- and epsilon-subunit gene expression.
abstract: Five different subunits, alpha, beta, gamma, delta and epsilon, constitute the acetylcholine receptors from mammalian skeletal muscle. Their corresponding mRNA levels are regulated differentially. In particular, mRNAs encoding the gamma- and epsilon-subunits, which specify two AChR isoforms, show a reciprocal behaviour during synapse formation and maturation. We have isolated 5' flanking sequences of the gamma- and epsilon-subunit genes that confer muscle-specific expression upon transient transfection of primary cultures of rat muscle cells. The gamma-subunit gene fragment contains two adjacent CANNTG sequence motifs that are essential for muscle-specific transcriptional activity suggesting transactivation by helix-loop-helix proteins. The epsilon-subunit gene fragment carries only a single CANNTG consensus motif which is not required for expression in transfected muscle cells. This sequence motif is, however, necessary to repress transcriptional activity in non-muscle cells and thus may control the muscle-specific expression of the epsilon-subunit gene. The results suggest that CANNTG motifs together with their 3' and 5' flanking nucleotides provide binding sites for both activating as well as repressing trans-acting factors. These elements could thus contribute to the muscle-specific expression of AChR subunit genes.
authors.affiliation: Max-Planck-Institut für medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, FRG.
authors.forename: M
authors.initials: M
authors.lastname: Numberger
authors.forename: I
authors.initials: I
authors.lastname: Dürr
authors.forename: W
authors.initials: W
authors.lastname: Kues
authors.forename: M
authors.initials: M
authors.lastname: Koenen
authors.forename: V
authors.initials: V
authors.lastname: Witzemann
mesh_terms: D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000378:metabolism*; D017570:MyoD Protein; D018008:Myogenin; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011950:Receptors, Cholinergic / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D014162:Transfection
chemical_list: C503799:MYOG protein, human; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503803:Myog protein, rat; D018008:Myogenin; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D015534:Trans-Activators; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase