Regulation of the rapsyn promoter by kaiso and delta-catenin.

Rodova M, Kelly KF, VanSaun M, Daniel JM, Werle MJ
Mol Cell Biol. 2004 24 (16): 7188-96

PMID: 15282317 · PMCID: PMC479716 · DOI:10.1128/MCB.24.16.7188-7196.2004

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.

MeSH Terms (26)

Active Transport, Cell Nucleus Animals Antibiotics, Antineoplastic Armadillo Domain Proteins Base Sequence Catenins Cell Adhesion Molecules Cell Line Chickens Cytoskeletal Proteins Fatty Acids, Unsaturated Gene Expression Regulation Genes, Reporter Humans Macromolecular Substances Mice Molecular Sequence Data Muscle, Skeletal Muscle Fibers, Skeletal Muscle Proteins Myasthenic Syndromes, Congenital Neuromuscular Junction Phosphoproteins Promoter Regions, Genetic Sequence Alignment Transcription Factors

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