DNA methylation status of myelinating Schwann cells during development and in diabetic neuropathy [Gene Expression Array: C57Bl6J mice]

DNA methylation is a key epigenetic regulator of mammalian embryogenesis and somatic cell differentiation. Using high-resolution genome-scale maps of methylation patterns, we show that the formation of myelin in the peripheral nervous system, proceeds with progressive DNA demethylation, which coincides with an upregulation of critical genes of the myelination process. More importantly, we found that, in addition to expression of DNA methyltransferases and demethylases, the levels of S-adenosylmethionine (SAMe), the principal biological methyl donor, could also play a critical role in regulating DNA methylation during myelination and in the pathogenesis of diabetic neuropathy. In summary, this study provides compelling evidence that SAMe levels need to be tightly controlled to prevent aberrant DNA methylation patterns, and together with recently published studies on the influence of SAMe on histone methylation in cancer and embryonic stem cell differentiation show that in diverse biological processes, the methylome, and consequently gene expression patterns, are critically dependent on levels of SAMe.

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Varela-Rey M, Iruarrizaga-Lejarreta M, Lozano JJ, Aransay AM, Fernandez AF, Lavin JL, Mósen-Ansorena D, Berdasco M, Turmaine M, Luka Z, Wagner C, Lu SC, Esteller M, Mirsky R, Jessen KR, Fraga MF, Martínez-Chantar ML, Mato JM, Woodhoo A