More importantly, the enzymatic activity of DNMT3A functions during hypoxia to demethylate the genomic DNA (Fig. S4) including the TWIST1 (Figs. 2c and 6d) and SNAIL1 promoter (data not shown).The upregulation of TWIST1 gene by DNMT3A-mediated promoter DNA demethylation in SW480 cells (Figs. 2c and 6d) is in correlation with the inverse relationship between the expression level and promoter methylation state of TWIST1 gene in colon cancer cell lines [31]. This evidence concerns the gene TWIST1 and malignant colon neoplasm.