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Neuron. 2014 Mar 5;81(5):1024-39. doi: 10.1016/j.neuron.2014.01.037.

S-adenosylmethionine levels regulate the schwann cell DNA methylome.

Author information

1
CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain.
2
Bioinformatic Platform, CIBERehd, Centre Esther Koplovitz (CEK), C/Rosselló 153 Subsuelo, 08036 Barcelona, Spain.
3
Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA-HUCA), Universidad de Oviedo, 33006 Oviedo, Spain.
4
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 09908 Catalonia, Spain.
5
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
6
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0146, USA.
7
Division of Gastrointestinal and Liver Diseases, USC Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
8
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 09908 Catalonia, Spain; Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, 08010 Catalonia, Spain.
9
Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA-HUCA), Universidad de Oviedo, 33006 Oviedo, Spain; Department of Immunology and Oncology, National Center for Biotechnology, CNB-CSIC, Cantoblanco, E-28049Madrid, Spain.
10
CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain; Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), P.O. Box 644, E-48080 Bilbao, Spain.
11
CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain; IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain. Electronic address: awoodhoo@cicbiogune.es.

Abstract

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 principal methyl donor in cytosine methylation, regulates the methylome dynamics during this process. Our studies also point to a possible role of SAMe in establishing the aberrant DNA methylation patterns in a mouse model of diabetic neuropathy, implicating SAMe in the pathogenesis of this disease. These critical observations establish a link between SAMe and DNA methylation status in a defined biological system, providing a mechanism that could direct methylation changes during cellular differentiation and in diverse pathological situations.

PMID:
24607226
PMCID:
PMC3960855
DOI:
10.1016/j.neuron.2014.01.037
[Indexed for MEDLINE]
Free PMC Article
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