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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 27, 2014 |
| Title |
DNA methylation status of myelinating Schwann cells during development and in diabetic neuropathy [Gene Expression Array: C57Bl6J mice] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Sciatic nerves from C57Bl6J mice of either sex, were dissected and pooled together at different developmental stages, 3 replicates per sample group.
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| Contributor(s) |
Woodhoo A, Lavin JL |
| Citation(s) |
24607226 |
| Submission date |
Apr 02, 2013 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Jose Luis Lavin |
| E-mail(s) |
joluito@gmail.com
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| Organization name |
CIC bioGUNE
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| Street address |
Parque Tecnológico de Bizkaia Building 502, Floor 0
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| City |
Derio |
| State/province |
Bizkaia |
| ZIP/Postal code |
48160 |
| Country |
Spain |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE45702 |
DNA methylation status of myelinating Schwann cells during development and in diabetic neuropathy |
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| Relations |
| BioProject |
PRJNA195900 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45700_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE45700_non-normalized.txt.gz |
2.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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