MULTIPLE ISOFORMS OF DNA METHYLTRANSFERASE ARE ENCODED BY THE VERTEBRATE CYTOSINE DNA METHYLTRANSFERASE GENE

This manuscript tests the hypothesis that multiple forms of cytosine-D NA methyltransferase (MeTase) are expressed in vertebrates in vivo. Ve rtebrate genomes are distinguished by tissue- tend gene-specific DNA m ethylation patterns. Specific methylation patterns are believed to enc ode epigenetic information. In distinction from the remarkable diversi ty of DNA methylation patterns, only one functional DNA MeTase cDNA ha s been identified to date in different vertebrate organisms. Using rev erse transcription-polymerase chain reaction and RNase protection anal yses, we show that the methyltransferase domain of the rat DNA MeTase is alternatively spliced in vivo, generating different in-frame varian ts 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 to ward a new mechanism for generating diversity of DNA MeTases and possi bly diverse DNA methylation patterns.