| p63 is a transcription factor predominantly expressed in basally located cells of epithelial tissues, where it acts as a critical regulator of biological programs. However, the full gamut of its regulatory functions and the mechanisms by which p63 executes them in epithelial cells are not well understood. The purpose of our study was to identify and analyze the transcriptional program regulated by p63 in normal human epithelial cells. The scope of our research has included: (i) determining the optimal consensus DNA binding site recognized by p63; (ii) mapping p63 response elements in regulatory regions of human genes; (iii) identifying genes regulated by p63 in normal epithelial cells; (iv) examining the functional profiles statistically over-represented in p63-regulated genes; (v) studying the effects of p63 loss-of-function in mammary epithelial cells; and (vi) performing clustering analyses of epithelial carcinomas based on their expression of p63-regulated genes. Overall, our studies contribute a panel of candidate genes regulated by p63 in normal epithelium, and provide insight to the specific mechanisms and pathways used by p63 to mediate its signaling. Aberrant control of p63 target genes in epithelial cells may confer properties associated with oncogenic transformation, and provide a molecular explanation for the prevalent deregulation of p63 expression in some epithelial carcinomas. |
