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Brain. 2013 Oct;136(Pt 10):3018-27. doi: 10.1093/brain/awt237. Epub 2013 Sep 11.

DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease.

Author information

1
1 Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet, Barcelona, Catalonia, Spain.

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.

KEYWORDS:

Alzheimer’s disease; DNA methylation; brain regions; epigenetics

PMID:
24030951
PMCID:
PMC3784285
DOI:
10.1093/brain/awt237
[Indexed for MEDLINE]
Free PMC Article

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