title: DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease.
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.
authors.affiliation: 1 Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet, Barcelona, Catalonia, Spain.
authors.forename: Jose V
authors.initials: JV
authors.lastname: Sanchez-Mut
authors.forename: Ester
authors.initials: E
authors.lastname: Aso
authors.forename: Nicolas
authors.initials: N
authors.lastname: Panayotis
authors.forename: Ira
authors.initials: I
authors.lastname: Lott
authors.forename: Mara
authors.initials: M
authors.lastname: Dierssen
authors.forename: Alberto
authors.initials: A
authors.lastname: Rabano
authors.forename: Rocio G
authors.initials: RG
authors.lastname: Urdinguio
authors.forename: Agustin F
authors.initials: AF
authors.lastname: Fernandez
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: Jose I
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Balazs
authors.initials: B
authors.lastname: Balint
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
authors.forename: Antonio
authors.initials: A
authors.lastname: Gomez
authors.forename: Cecile
authors.initials: C
authors.lastname: Gurnot
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Roux
authors.forename: Jesus
authors.initials: J
authors.lastname: Avila
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D004247:DNA / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA
keywords: Alzheimer’s disease; DNA methylation; brain regions; epigenetics
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