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Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases

Nature Genetics volume 19, pages 219–220 (1998)Cite this article

De novo methylation of genomic DNA is a developmentally regulated process that is believed to play a pivotal role in regulation of genomic imprinting and X-chromosome inactivation in mammals1,2,3. Aberrant de novo methylation of growth regulatory genes has been associated with tumorigenesis in humans4,5,6. We have shown previously that de novo methylation persists in embryonic stem (ES) cells lacking Dnmt1, which encodes the constitutive DNA methyltransferase Dnmt1 (or MT1), indicating the existence of independently encoded de novo methyltransferases7.

Dnmt3a transcripts of 4.2 kb, corresponding to cDNA size, were expressed abundantly in ES cells, but at very low levels in differentiated embryoid bodies or adult tissues (Fig. 1c, upper panel). With polyA+ RNA blots, 9.5-kb transcripts were detected in adult tissues and embryos, whereas the 4.2-kb transcripts were weakly expressed in most tissues except embryonic day (E) 10.5 embryos (Fig. 1c, lower panel). The 9.5-kb transcripts may contain large 5´ UTRs, as none of the cDNA or EST clones analysed contain alternatively spliced exons. Transcriptional regulation of Dnmt3a and the function of different transcripts in development need to be investigated. Dnmt3b is also highly expressed in undifferentiated ES cells. The 4.4-kb Dnmt3b transcripts, however, were barely detected in differentiated cells and adult tissues except testes (Fig. 1c).

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Figure 1: Sequence alignments, structures and expression patterns of mouse Dnmt3a and Dnmt3b.
Figure 2: De novo and maintenance methyltransferase activities of Dnmt3α and Dnmt3β.

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Acknowledgements

We thank P. Oh for the ES cell RNA blot. This work was supported by grants from NIH (GM52106) and Bristol Myers-Squibb to E.L. M.O. was a postdoctoral fellow of the Japan Society for the Promotion of Science.

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    1. Department of Medicine, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

      Masaki Okano, Shaoping Xie & En Li

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    Correspondence to En Li.

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    Okano, M., Xie, S. & Li, E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19, 219–220 (1998). https://doi.org/10.1038/890

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