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- and 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.
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
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Deng
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Szyf
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology; D002454:Cell Differentiation; D015257:DNA-Cytosine Methylases / Q000235:genetics*; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D007438:Introns; D007527:Isoenzymes / Q000235:genetics*; D008099:Liver / Q000196:embryology / Q000201:enzymology; D008969:Molecular Sequence Data; D016716:PC12 Cells; D012322:RNA Precursors / Q000378:metabolism; D051381:Rats; D016364:Reading Frames; D014018:Tissue Distribution
D007527:Isoenzymes; D012322:RNA Precursors; D015257:DNA-Cytosine Methylases