The Promyelocytic Leukemia Zinc Finger (PLZF ) gene is a novel transcriptional target of the CCAAT-Displacement-Protein (CUX1) repressor

The CCAAT-Displacement-Protein (CUX1) can transcriptionally repress sucrase-isomaltase gene expression, a specific product of enterocytes that becomes re-expressed during human colonic polyposis. Little is known of the gene repertoire that is directly affected by CUX1 in the intestinal epithelial context. This article identifies the Promyelocytic Leukemia Zinc Finger (PLZF) gene as a transcriptional target for the CUX1 repressor. CUX1 interacts in vivo with multiple DNA-binding sites in the 5'-UTR and promoter of the PLZF gene in colorectal cancer cells, a region that is functionally targeted by CUX1 in cotransfection assays. PLZF was found to be induced in colorectal cancer cell lines, correlating with a low detectable level of CUX1, a pattern that was reversed in normal human colonocytes. Reduction of p200CUX1 expression by RNAi in the Caco-2/15 cell line increased PLZF gene transcript expression. Because of the implication of Plzf in the regulation of stem cell maintenance, as well as Wnt and Ras signaling, in other systems, our observations suggest that the novel genetic relationship between CUX1 and PLZF could be of relevance to human diseases, such as leukemia, and open up a new field of investigation for the implication of these regulators during intestinal polyposis and cancer.