Signaling crosstalk between the beta-catenin and NF-kappa B pathways represents a functional network. To test whether the crosstalk also occurs on their common target genes, the cyclin D1 promoter was used as a model because it contains binding sites for both proteins. beta-catenin activated transcription from the cyclin D1 promoter, while co-expression of NF-kappa B p65 reduced beta-catenin-induced transcription. Chromatin immunoprecipitation revealed lithium chloride-induced binding of beta-catenin on one of the T-cell activating factor binding sites. More interestingly, beta-catenin binding was greatly reduced by NF-kappa B p65, possibly by the protein-protein interaction between the two proteins. Such a dynamic and complex binding of beta-catenin and NF-kappa B on promoters might contribute to the regulated expression of their target genes. (C) 2010 Elsevier Inc. All rights reserved.