Quiescence specific β-catenin transcriptional networks in myogenic cells

Wnt/β-catenin signaling is active during cellular quiescence in muscle myoblasts. Exposure of quiescent myoblasts to Wnt3a led to deregulation of genes associated with both myogenic differentiation and proliferation. Genome-wide analysis Ctnnb1 by ChIP-chip revealed quiescence-specific enrichment on genes of multiple functional classes. The major class of genes bound by Ctnnb1were Wnt pathway genes and all occupied promoters were highly enriched for TCF DNA binding motifs. Cross-comparison of ChIP-Chip with transcriptome data revealed both transcriptional activation as well as repression in Ctnnb1 occupied genes. Inhibition of Ctnnb1-mediated transactivation using shRNA and pharmacological agents led to de-regulation of the quiescence-associated transcriptional profile. Ctnnb1 binding is associated with repression of myogenic genes and cell cycle progression factors while maintaining differential response by these genes to Wnt signaling during quiescence.

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