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

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Author
Sanchez-Mut, Jose V.
Aso, Ester
Panayotis, Nicolas
Lott, Ira
Dierssen, Mara
Rabano, Alberto
Urdinguio, Rocio G.
Fernandez, Agustin F.
Astudillo, Aurora
Martin-Subero, Jose I.
Balint, Balazs
Fraga, Mario F.
Gomez, Antonio
Gurnot, Cecile
Roux, Jean-Christophe
Avila, Jesus
Ferrer, Isidre
Esteller, Manel
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1093/brain/awt237Metadata
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Sanchez-Mut, J. V., E. Aso, N. Panayotis, I. Lott, M. Dierssen, A. Rabano, R. G. Urdinguio, et al. 2013. “DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease.” Brain 136 (10): 3018-3027. doi:10.1093/brain/awt237. http://dx.doi.org/10.1093/brain/awt237.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784285/pdf/Terms of Use
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