Methylation at the 5'-position of cytosine is the only known naturally occurring covalent modification of the mammalian genome. DNA methylation requires the enzymatic activity of DNA 5-cytosine methyltransferase (Dnmt) proteins, which catalyze the transfer of a methyl group from S-adenosyl methionine to the 5'-position of cytosines, thereby repressing expression of the target gene. Dnmt3L (DNA (cytosine-5)-methyltransferase 3-like) is a 387 amino acid protein that contains one ADD-type zinc finger and is a member of the Dnmt family. Localized to the nucleus and expressed at lows levels in thymus, testis and ovary, Dnmt3L does not exhibit DNA methyltransferase activity, but is able to stimulate de novo methylation by Dnmt3 and is thought to play a key role in the establishment of genomic imprints. Additionally, Dnmt3L interacts with histone deacetylase 1 (HDAC1) and, through this interaction, mediates transcriptional repression. Multiple isoforms of Dnmt3L exist due to alternative splicing events.