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Transcription factor AP2C (TFAP2C) is believed to be involved in breast cancer carcinogenesis. However, the molecular mechanisms of regulating its trans-activation activity are not well understood. One of the potential mechanisms is through p53-mediated regulation. Using ChIP-seq analysis to map the TFAP2C occupancy across the genome, we found that the introduction of p53 to HCT 116 p53 -/- colon cancer cell line significantly augments TFAP2C occupancy on the promoter regions of a group of genes. Of these, six genes were further investigated. First, TFAP2C binding sites were identified in the center of ChIP-seq peaks on the promoters of the six genes and these were verified by gel shift assays. One of these genes, MUC1, was then determined to be activated by TFAP2C in MCF-7 breast cancer cell line. Subsequently, MUC1 was selected as the model target gene to elucidate the mechanism for p53-mediated enhancement of TFAP2C occupancy. We hypothesized that DNA methylation of the MUC1 promoter is altered by p53, leading to the increased TFAP2C occupancy to its TFBS on MUC1 promoter. To examine this, CpG methylation assay was performed. The result showed the DNA methylation of MUC1 promoter region remains identical with or without over-expression of p53 in HCT 116 p53 -/- cell line. From these studies, I conclude that 1) introduction of p53 augments TFAP2C binding on specific gene targets; 2) MUC1 gene is activated by TFAP2C and two TFAP2C binding sites were verified; 3) promoter DNA methylation does not explain the increased occupancy of TFAP2C on MUC1 promoter.