DNA methylation status of myelinating Schwann cells during development and in diabetic neuropathy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Jose Lavin
PROVIDER: E-GEOD-45702 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description: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 developmental Schwann cell myelination, GNMT-KO and diabetic mice were generated by Reduced-Representation Bisulfite Sequencing, with 2-3 replicates per sample group.
2014-01-27 | E-GEOD-45343 | biostudies-arrayexpress
Project description: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.
2014-01-27 | E-GEOD-51031 | biostudies-arrayexpress
Project description: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. Axonal myelination by Schwann cells in the peripheral nervous system is essential for rapid saltatory impulse conduction, and malformation or destruction of myelin sheaths can lead to severe motor and sensory disabilities (peripheral neuropathies). Using high-resolution genome-scale methylome maps, we found that DNA methylation could play a critical role in the generation of myelinated Schwann cells. This process was accompanied by a global DNA demethylation at most genomic elements. Notably, demethylation at gene-regulatory regions was associated with activation of critical myelination-specific genes. Furthermore, we found an aberrant DNA methylation pattern in a mouse model of diabetic neuropathy, which could be involved in the pathogenesis of the disease. Importantly, we found that these methylation patterns in both situations could be regulated by levels of S-adenosylmethionine (SAMe), the principal biological methyl donor. Together with recent studies on the influence of SAMe on histone methylation in diverse biological processes, we conclude that the methylation landscape of cells could be critically dependent on levels of SAMe. These provide a mechanistic link between metabolism and gene regulatory networks in normal and pathological situations. Sciatic nerves from post natal day 90 GNMT (wt and KO) mice of either sex were dissected and pooled together, 2 replicates per sample group.
2014-01-27 | E-GEOD-45701 | biostudies-arrayexpress
Project description: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. Axonal myelination by Schwann cells in the peripheral nervous system is essential for rapid saltatory impulse conduction, and malformation or destruction of myelin sheaths can lead to severe motor and sensory disabilities (peripheral neuropathies). Using high-resolution genome-scale methylome maps, we found that DNA methylation could play a critical role in the generation of myelinated Schwann cells. This process was accompanied by a global DNA demethylation at most genomic elements. Notably, demethylation at gene-regulatory regions was associated with activation of critical myelination-specific genes. Furthermore, we found an aberrant DNA methylation pattern in a mouse model of diabetic neuropathy, which could be involved in the pathogenesis of the disease. Importantly, we found that these methylation patterns in both situations could be regulated by levels of S-adenosylmethionine (SAMe), the principal biological methyl donor. Together with recent studies on the influence of SAMe on histone methylation in diverse biological processes, we conclude that the methylation landscape of cells could be critically dependent on levels of SAMe. These provide a mechanistic link between metabolism and gene regulatory networks in normal and pathological situations. Sciatic nerves from C57Bl6J mice of either sex, were dissected and pooled together at different developmental stages, 3 replicates per sample group.
2014-01-27 | E-GEOD-45700 | biostudies-arrayexpress
Project description:We compared gene expression at ages P4 and P60 in sciatic nerve of wild type mice and mice with peripheral neuropathies caused by altered Pmp22 gene dosage (homozygous knockout or transgene) or a point mutation (Trembler).
2007-11-03 | E-GEOD-1947 | biostudies-arrayexpress
Project description:Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs), a dermally-derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally-derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from facial (neural crest-derived) and foreskin (mesodermally-derived) dermis, and the mesodermally-derived SKPs can make myelinating Schwann cells. Thus, non-neural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally-defined lineage boundaries are more flexible than widely thought. We obtained 3 independent samples of nerve Schwann cells, SKP-derived Schwann cells, and Dorsal Trunk SKPs, each, from adult SD rats. Primary cells were isolated and cultured, and RNA was collected from those cultured samples. RNA samples deriving from these cells were analyzed on the Affymetrix Rat Gene 1.0 ST Array.
2014-08-01 | E-GEOD-57505 | biostudies-arrayexpress
Project description:Identify mRNA targets of the RNA-binding protein HuR in vivo during Schwann cell development using RIP-chip analysis. IP protocol of endogenous mRNA-transfected HuR complexes was performed as described in Keene et al. (2006). In brief, 500 mg of whole-cell lysate obtained from a pool of NB or P5 sciatic nerves from C57BL6J mice were incubated with a suspension of Protein Sepharose beads (Sigma-Aldrich), pre-coated with 15 mg of either IgG1 (BD Pharmingen) or anti-HuR (Santa Cruz Biotechnology) antibodies. mRNAs were isolated using the phenol-chloroform method.
2012-01-19 | E-MEXP-3519 | biostudies-arrayexpress
Project description:Two mouse lines, OE/+ and OE/OE were generated expressing graded elevation (6 fold and 28 fold, respectively) of c-Jun protein selectively in Schwann cells. The effects of this on global gene expression and cellular structure in uninjured nerves was analysed during development and in the adult. Changes in gene expression and cellular arrangements were mild but detectable in c-Jun OE/+ mice, while nerves in c-Jun OE/OE mice showed obvious de-myelination and gene expression changes, including up- and down-regulation of genes previously shown to be controlled by c-Jun in Schwann cells.
2017-10-16 | E-MTAB-6138 | biostudies-arrayexpress
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2014-08-01 | E-GEOD-57519 | biostudies-arrayexpress
Project description:Egr2/Krox20 and Sox10 regulate genes involved in formation of myelination in the peripheral nervous system. ChIP-chip assays were performed on rat sciatic nerve at P15, a peak timepoint of myelination. In addition, Faire was used to identify areas of open chromatin. This experiment includes a custom ChIP-chip design incorporating many genes that are dynamically regulated during peripheral nerve myelination. Two antibodies were used for Egr2, Abcam and Covance PRB-236P. Egr2 and Sox10 ChIP samples were hybridized along with total input. In addition, FAIRE samples were hybridized relative to input DNA
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