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This study delineates epigenomic and transcriptomic analysis of Forkhead box transcription factor FOXD2 in intestinal stem cell and colon cancer. By the anslysis of extensive mutiomics databases, FOXD2 was identified as a chromatin tuning factor to suppress cancer development. Here, we provide genome-wide maps of histone modifications and chromatin structures and interactions as well as gene expression profiles on FOXD2 overexpression.