Moreover, EVI1 forms complexes with the 2 de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B via its proximal zinc finger domain and mediates de novo DNA methylation of target regions.60 The phosphorylation site at S436 of the EVI1 protein seems to be important for the interaction with DNMT3A.10 With regards to this interaction with DNMTs, it is interesting to note that high expression of EVI1 in AML correlates with a distinct hypermethylation signature.61 This signature is characterized by hypermethylated CpG-rich promoter regions that are enriched for EVI1 binding sites. This evidence concerns the gene MECOM and acute myeloid leukemia.