CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. DNMT3A encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. Alternative splicing results in multiple transcript variants encoding different isoforms.The mouse genes, termed Dnmt3a and Dnmt3b, show little sequence similarity to mouse Dnmt1 and Dnmt2, and masc1 from Ascobolus. The Dnmt3a cDNA encodes a protein of 908 amino acids. The human DNMT3A and DNMT3B cDNAs are highly homologous to the mouse genes. Dnmt3a and Dnmt3b transcripts were abundantly expressed in undifferentiated embryonic stem cells.