Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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DNA methylation status of myelinating Schwann cells during development and in diabetic neuropathy [Bisulfite-Seq2]


ABSTRACT: 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. DNA methylome maps of mouse Schwann cells in which GNMT was silenced by lentiviral vectors, cultured in normal medium or low methionine medium.

ORGANISM(S): Mus musculus

SUBMITTER: Jose Lavin 

PROVIDER: E-GEOD-51031 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications


Axonal myelination is essential for rapid saltatory impulse conduction in the nervous system, and malformation or destruction of myelin sheaths leads to motor and sensory disabilities. DNA methylation is an essential epigenetic modification during mammalian development, yet its role in myelination remains obscure. Here, using high-resolution methylome maps, we show that DNA methylation could play a key gene regulatory role in peripheral nerve myelination and that S-adenosylmethionine (SAMe), the  ...[more]

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