A search by Okano's group51 for expressed sequence tags using full-length bacterial methyltransferase sequences as queries identified two methyltransferase motifs in both mouse and human EST databases. The mouse genes were named Dnmf3a and Dnmf3b because they showed little sequence similarity to either Dnmfl or Dnmf2. Dnmf3A and Dnmf3B cDNAs of mice encode proteins of 909 and 859 amino acids; Dnmf3B also encoded shorter polypeptides of 840 and 777 amino acid residues through alternative splicing.
Dnmf3a and Dnmf3b were both expressed abundantly in undifferentiated cells, but at low levels in differentiated embryonic stem cells and adult mouse tissues, and both showed equal activity toward hemimethylated and unmethylated DNA. The expression pattern plus the substrate selectivity suggested that Dnmf3a and Dnmf3b might encode de novo methyltransferases.51
The human homologs, DNMT3A and DNMT3B, were highly homologous to the mouse genes. DNMT3A and DNMT3B mapped to human chromosomes 2p and 20q, and encoded proteins of 912 and 865 amino acids, respectively40 (Figure 6.4). A human disorder has been attributed to mutations in DNMT3B (see p. 164).
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