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

被引：104

作者：

Sanchez-Mut, Jose V. ^{[1
]}

Aso, Ester ^{[2
]}

Panayotis, Nicolas ^{[3
,4
]}

Lott, Ira ^{[5
]}

Dierssen, Mara ^{[6
,7
]}

Rabano, Alberto ^{[8
]}

Urdinguio, Rocio G. ^{[9
]}

Fernandez, Agustin F. ^{[9
]}

Astudillo, Aurora ^{[10
]}

Martin-Subero, Jose I. ^{[1
]}

Balint, Balazs ^{[1
]}

Fraga, Mario F. ^{[9
,11
]}

Gomez, Antonio ^{[1
]}

Gurnot, Cecile ^{[12
]}

Roux, Jean-Christophe ^{[3
,4
]}

Avila, Jesus ^{[13
,14
]}

Hensch, Takao K. ^{[12
]}

Ferrer, Isidre ^{[2
]}

Esteller, Manel ^{[1
,15
,16
]}

机构：

[1] Bellvitge Biomed Res Inst IDIBELL, PEBC, Barcelona, Catalonia, Spain

[2] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Hosp Univ Bellvitge, Neuropathol Inst,Bellvitge Biomed Res Inst IDIBEL, Barcelona, Catalonia, Spain

[3] Fac Med La Timone, INSERM UMR S 910, Unite Genet Med & Genom Fonct, F-13385 Marseille, France

[4] Aix Marseille Univ, Fac Med La Timone, F-13000 Marseille, France

[5] Univ Calif Irvine, Sch Med, Dept Paediat & Neurol, Orange, CA 92868 USA

[6] UPF, CRG, E-08003 Barcelona, Spain

[7] CIBERER, E-08003 Barcelona, Spain

[8] Fdn CIEN, Neuropathol Lab, Res Unit Alzheimers Project UIPA, Madrid, Spain

[9] Univ Oviedo, HUCA, Inst Oncol Asturias IUOPA, Canc Epigenet Lab, E-33006 Oviedo, Spain

[10] Univ Oviedo, IUOPA, Banco Tumores, HUCA, E-33006 Oviedo, Spain

[11] Natl Biotechnol Ctr, Dept Immunol & Oncol, Madrid 28049, Spain

[12] Harvard Univ, Ctr Brain Sci, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[13] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Dept Neurosci, Madrid, Spain

[14] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

[15] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Catalonia, Spain

[16] ICREA, Barcelona, Catalonia, Spain

来源：

BRAIN | 2013年 / 136卷

关键词：

DNA methylation; Alzheimer's disease; brain regions; epigenetics; AXON INITIAL SEGMENTS; BETA-IV-SPECTRIN; EPIGENETIC MECHANISMS; PROTEIN; EXPRESSION; ACTIVATION; NEURONS; THROMBOXANE-A(2); SUPPRESSION; SIGNATURES;

D O I：

10.1093/brain/awt237

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：3018 / 3027

页数：10

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