A missense mutation (Dnmt3aD329A) in the PWWP targeting domain of DNMT3A can result in hypermethylation of CGI in mice particularly at CGI promoters and gene bodies marked by H3K27me3, representing an alternative hypermethylation pathway which may be utilised in specific cancer contexts such as acute myeloid leukaemia [67]. The gene discussed is DNMT3A; the disease is cancer.