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

Authors :
Sanchez-Mut JV
Aso E
Panayotis N
Lott I
Dierssen M
Rabano A
Urdinguio RG
Fernandez AF
Astudillo A
Martin-Subero JI
Balint B
Fraga MF
Gomez A
Gurnot C
Roux JC
Avila J
Hensch TK
Ferrer I
Esteller M
Source :
Brain : a journal of neurology [Brain] 2013 Oct; Vol. 136 (Pt 10), pp. 3018-27. Date of Electronic Publication: 2013 Sep 11.
Publication Year :
2013

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.

Details

Language :
English
ISSN :
1460-2156
Volume :
136
Issue :
Pt 10
Database :
MEDLINE
Journal :
Brain : a journal of neurology
Publication Type :
Academic Journal
Accession number :
24030951
Full Text :
https://doi.org/10.1093/brain/awt237