In order to evaluate the consequences of combined EZH2 and DNMT inhibition on the epigenome of MM, we utilised ChIP-seq combined with Illumina Infinium MethylationEPIC arrays and RNA-seq. Our data revealed a reduction of DNA methylation in active enhancer regions, while regions classified as Polycomb and bivalent TSS/enhancer showed a reduction of H3K27me3. Here, EZH2 is linked to Miyoshi myopathy.