The Dnmt2 Family

Dnmtl was the only DNA methyltransferase identified in mammals for about a decade following its cloning and sequencing. Several other groups sought new candidate DNA methyltransferases in mammals by searching expressed sequence tag (EST) databases. Yoder and Bestor48 reported another potential DNA methyltransferase (pmtl+) in 1998 in fission yeast, an organism not known to methy-late its DNA. Bestor also showed that disruption of Dnmt2, the mouse homolog of the yeast enzyme, had no discernible effect on methylation patterns of embryonic stem cells, nor did it affect the ability of such cells to methylate newly integrated retroviral DNA.40

About the same time, Van den Wygaert and colleagues reported the identification and characterization of the human DNMT2 gene.49 Sequence analysis indicated that DNMT2 encoded 391 amino acid residues, but lacked a large part of the N-terminus that is usually involved in the targeting and regulation of the MTases. The protein overexpressed in bacteria did not show any DNA methyl-transferase activity. Mapping by fluorescent /n s/fw hybridization (FISH) showed the DNMT2 gene was located on human chromosome 10p13-22. Tissue-specific expression revealed the human enzyme was relatively high in placenta, thymus, and testis. However, DNMT2 was overexpressed in several cancer cell lines consistent with the role of DNA methylation in cancer.

A more recent report has identified and analyzed the human homolog, DNMT2.50 The purified enzyme had weak DNA methyltransferase activity at CG sites. Limited data indicated DNMT2 recognized CG sites in a palindromic TTCCGGAA sequence context (Figure 6.4).

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