In this model, abnormal enhancer activity (Enhancer3 in HCT116, and Enhancer1 and Enhancer3 in RKO cells) of CYR61 occurs in CRC and up-regulates the expression of CYR61. Based on the crucial role of Mediator in the organization of genomic DNA topological structure [48] and a recent study showing that FOXA1 is essential for the recruitment of Mediator [49], we speculate that, under our conditions, the Mediator complex is likely to contribute to the role of FOXA1 and CBP in long-range looping. Here, CREBBP is linked to colorectal carcinoma.