DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease
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- dc.contributor.author Sanchez-Mut, Jose V.
- dc.contributor.author Dierssen Sotos, Mara
- dc.contributor.author Esteller, Manel
- dc.date.accessioned 2025-01-13T08:34:19Z
- dc.date.available 2025-01-13T08:34:19Z
- dc.date.issued 2013
- dc.description.abstract The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation is a major regulator of transcriptional activity, and aberrations in the distribution of this epigenetic mark may be involved in many neurological disorders, such as Alzheimer’s disease. Herein, we have analysed 12 distinct mouse brain regions according to their CpG 5’-end gene methylation patterns and observed their unique epigenetic landscapes. The DNA methylomes obtained from the cerebral cortex were used to identify aberrant DNA methylation changes that occurred in two mouse models of Alzheimer’s disease. We were able to translate these findings to patients with Alzheimer’s disease, identifying DNA methylation-associated silencing of three targets genes: thromboxane A2 receptor (TBXA2R), sorbin and SH3 domain containing 3 (SORBS3) and spectrin beta 4 (SPTBN4). These hypermethylation targets indicate that the cyclic AMP response element-binding protein (CREB) activation pathway and the axon initial segment could contribute to the disease.en
- dc.description.sponsorship This work was supported by the Human Frontiers Science Program (HFSP) Ref.RGP0018/2007-C, the European Community’s Sixth Framework Programme (FP7/2007-2013) under grant agreement PITN-GA-2009-238242—DISCHROM project and grant agreement 278486-DEVELAGE, NIH Grants NIA P50-AG16573 and HD065160-01, the Instituto de Salud Carlos III—Ministerio de Sanidad y Consumo Proyecto FIS (Fondo Investigación Sanitaria, Spain) through the E-RARE EuroRETT network and CureFXS ERare-EU/FIS PS09102673, Grants P50-AG16573, HD065160-01 and SAF2007-6-8, the Fondation Lejeune (France), the Lilly Foundation (Spain), the Lilly Foundation (Spain), Botin Foundation, and the Cellex Foundation (Catalonia). J.V.S-M is affiliated to the Neuroscience PhD program of the Autonomous University of Barcelona, Spain. ME is an ICREA Reseah Professor.en
- dc.format.mimetype application/pdf
- dc.identifier.citation Sanchez-Mut JV, Aso E, Panayotis N, Lott I, Dierssen M, Rabano A, et al. DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease. Brain. 2013 Oct;136(10):3018-27. DOI: 10.1093/brain/awt237
- dc.identifier.doi http://dx.doi.org/10.1093/brain/awt237
- dc.identifier.issn 1460-2156
- dc.identifier.uri http://hdl.handle.net/10230/69059
- dc.language.iso eng
- dc.publisher Oxford University Press
- dc.relation.ispartof Brain. 2013 Oct;136(10):3018-27
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/238242
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/278486
- dc.rights © The Author (2013). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc/3.0/
- dc.subject.keyword DNA methylationen
- dc.subject.keyword Alzheimer’s diseaseen
- dc.subject.keyword Brain regionsen
- dc.subject.keyword Epigeneticsen
- dc.title DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion