Multiple isoforms of DNA methyltransferase are encoded by the vertebrate cytosine DNA methyltransferase gene

This manuscript tests the hypothesis that multiple forms of cytosine-DNA methyltransferase (MeTase) are expressed in vertebrates in vivo. Vertebrate genomes are distinguished by tissue- tend gene-specific DNA methylation patterns. Specific methylation patterns are believed to encode epigenetic information. In distinction from the remarkable diversity of DNA methylation patterns, only one functional DNA MeTase cDNA has been identified to date in different vertebrate organisms. Using reverse transcription-polymerase chain reaction and RNase protection analyses, we show that the methyltransferase domain of the rat DNA MeTase is alternatively spliced in vivo, generating different in-frame variants of DNA MeTase in specific tissues. This process is developmentally regulated and is induced in PC12 cells by a known inducer of neuronal differentiation, nerve growth factor. The data presented here point toward a new mechanism for generating diversity of DNA MeTases and possibly diverse DNA methylation patterns.