CEACAM1 , a SOX9 direct transcriptional target identified in the colon epithelium

A deletion of the transcription factor SOX9 gene in the mice intestine affects the morphology of the colon epithelium and leads to hyperplasia. Nevertheless, direct i transcriptional targets of SOX9 in this tissue are still unknown. A microarray analysis identified the tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) as a possible SOX9 target gene and we demonstrate here that SOX9 upregulates CEACAM1 in human colonic cells. Moreover, CEACAM1 expression is reduced in colon of SOX9-deficient mouse, suggesting an important function for SOX9 in the transcriptional activation of the CEACAM1 gene. We further identified SOX9-binding sequences in the human i and rat CEACAM1 promoters, and an electrophoretic mobility shift together with a chromatin immunoprecipitation provided an additional evidence of the SOX9 binding to the human promoter. In addition, we established that histone acyl-transferase p300 behaves as an SOX9 co-activator of the rat and human CEACAM1 promoters. These results highlight CEACAM1 as the first direct target of SOX9 identified in the colon epithelium.