Several striking discoveries that came from our ChIP-seq analysis of the 6 different cell lines are: i) TCF7L2 has multiple binding sites near each target gene; ii) TCF7L2 has developed cell type-specific mechanisms for regulating a set of approximately 14,000 genes; iii) TCF7L2 binds to more than 40% of the active enhancers in each of the 6 cancer cell lines; and iv) TCF7L2 functions as repressor when recruited to the genome via tethering by the master regulator GATA3. Here, TCF7L2 is linked to cancer.