title: S-adenosylmethionine levels regulate the schwann cell DNA methylome.
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.
authors.affiliation: CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Varela-Rey
authors.affiliation: CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Iruarrizaga-Lejarreta
authors.affiliation: Bioinformatic Platform, CIBERehd, Centre Esther Koplovitz (CEK), C/Rosselló 153 Subsuelo, 08036 Barcelona, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lozano
authors.affiliation: CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Aransay
authors.affiliation: Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA-HUCA), Universidad de Oviedo, 33006 Oviedo, Spain.
authors.forename: Agustín F
authors.initials: AF
authors.lastname: Fernandez
authors.affiliation: CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Lavin
authors.affiliation: CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Mósen-Ansorena
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 09908 Catalonia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Berdasco
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Turmaine
authors.affiliation: Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0146, USA.
authors.forename: Zigmund
authors.initials: Z
authors.lastname: Luka
authors.affiliation: Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0146, USA.
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.affiliation: 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.
authors.forename: Shelly C
authors.initials: SC
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Rhona
authors.initials: R
authors.lastname: Mirsky
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Kristján R
authors.initials: KR
authors.lastname: Jessen
authors.affiliation: 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.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
authors.affiliation: 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.
authors.forename: María L
authors.initials: ML
authors.lastname: Martínez-Chantar
authors.affiliation: CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park, Derio, 48160 Bizkaia, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Mato
authors.affiliation: 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.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Woodhoo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D023281:Genomics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009186:Myelin Sheath / Q000378:metabolism* / Q000502:physiology; D010525:Peripheral Nerves / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D012436:S-Adenosylmethionine