Regulation of the rapsyn promoter by kaiso and delta-catenin.
Rapsyn is a synapse-specific protein that is required for clustering acetylcholine receptors at the neuromuscular junction. Analysis of the rapsyn promoter revealed a consensus site for the transcription factor Kaiso within a region that is mutated in a subset of patients with congenital myasthenic syndrome. Kaiso is a POZ-zinc finger family transcription factor which recognizes the specific core consensus sequence CTGCNA (where N is any nucleotide). Previously, the only known binding partner for Kaiso was the cell adhesion cofactor, p120 catenin. Here we show that delta-catenin, a brain-specific member of the p120 catenin subfamily, forms a complex with Kaiso. Antibodies against Kaiso and delta-catenin recognize proteins in the nuclei of C2C12 myocytes and at the postsynaptic domain of the mouse neuromuscular junction. Endogenous Kaiso in C2C12 cells coprecipitates with the rapsyn promoter in vivo as shown by chromatin immunoprecipitation assay. Minimal promoter assays demonstrated that the rapsyn promoter can be activated by Kaiso and delta-catenin; this activation is apparently muscle specific. These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and delta-catenin. We propose a new model of synapse-specific transcription that involves the interaction of Kaiso, delta-catenin, and myogenic transcription factors at the neuromuscular junction.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, 66160-7421, USA.
Marianna
M
Rodova
Kevin F
KF
Kelly
Michael
M
VanSaun
Juliet M
JM
Daniel
Michael J
MJ
Werle
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D051186:Armadillo Domain Proteins; D001483:Base Sequence; D051177:Catenins; D015815:Cell Adhesion Molecules; D002460:Cell Line; D002645:Chickens; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics / Q000378:metabolism; D009469:Neuromuscular Junction / Q000502:physiology; D010750:Phosphoproteins; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism*; D000095002:Delta Catenin
D000903:Antibiotics, Antineoplastic; D051186:Armadillo Domain Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D005231:Fatty Acids, Unsaturated; D046911:Macromolecular Substances; D009124:Muscle Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; C492254:ZBTB33 protein, human; C118822:Zbtb33 protein, mouse; C051609:peripheral membrane protein 43K; C038753:leptomycin B; D000095002:Delta Catenin