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DOI | 10.1038/s41467-018-07527-w |
Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1 | |
Weber, Axel1; Schwarz, Sigrid C.2,3; Tost, Jorg4; Truembach, Dietrich5; Winter, Pia1; Busato, Florence4; Tacik, Pawel6,7; Windhorst, Anita C.8; Fagny, Maud4; Arzberger, Thomas3,9,10; McLean, Catriona11; van Swieten, John C.12; Schwarz, Johannes2; Weisenhorn, Daniela Vogt3,5,13; Wurst, Wolfgang3,5,13,14; Adhikary, Till15; Dickson, Dennis W.6; Hoelinger, Gunter U.2,3,14; Mueller, Ulrich1 | |
2018-07-26 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Germany; France; USA; Australia; Netherlands |
英文摘要 | Genetic, epigenetic, and environmental factors contribute to the multifactorial disorder progressive supranuclear palsy (PSP). Here, we study epigenetic changes by genome-wide analysis of DNA from postmortem tissue of forebrains of patients and controls and detect significant (P < 0.05) methylation differences at 717 CpG sites in PSP vs. controls. Four-hundred fifty-one of these sites are associated with protein-coding genes. While differential methylation only affects a few sites in most genes, DLX1 is hypermethylated at multiple sites. Expression of an antisense transcript of DLX1, DLX1AS, is reduced in PSP brains. The amount of DLX1 protein is increased in gray matter of PSP forebrains. Pathway analysis suggests that DLX1 influences MAPT-encoded Tau protein. In a cell system, overexpression of DLX1 results in downregulation of MAPT while overexpression of DLX1AS causes upregulation of MAPT. Our observations suggest that altered DLX1 methylation and expression contribute to pathogenesis of PSP by influencing MAPT. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000439809400009 |
WOS关键词 | TRANSCRIPTION FACTOR-BINDING ; GLUTAMIC-ACID DECARBOXYLASE ; ALZHEIMERS-DISEASE ; TAU PHOSPHORYLATION ; RISK LOCI ; GENE ; DIFFERENTIATION ; BRAIN ; EXPRESSION ; CELLS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204109 |
专题 | 资源环境科学 |
作者单位 | 1.Justus Liebig Univ, Inst Human Genet, D-35392 Giessen, Germany; 2.Tech Univ Munich, Dept Neurol, D-81377 Munich, Germany; 3.German Ctr Neurodegenerat Dis DZNE, D-81377 Munich, Germany; 4.CEA, Ctr Natl Rech Genom Humaine, Inst Biol Francois Jacob, Lab Epigenet & Environm, F-91000 Evry, France; 5.Helmholtz Ctr Munchen, Inst Dev Genet, D-85764 Munich, Germany; 6.Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA; 7.Univ Bonn, Med Ctr, Dept Neurodegenerat Dis & Geriatr Psychiat, D-53127 Bonn, Germany; 8.Justus Liebig Univ, Inst Med Informat, D-35392 Giessen, Germany; 9.Ludwig Maximilians Univ Munchen, Dept Psychiat, D-81377 Munich, Germany; 10.Ludwig Maximilians Univ Munchen, Ctr Neuropathol & Prion Res, D-81377 Munich, Germany; 11.Victorian Brain Bank, Alfred Anat Pathol & NNF, Carlton, Vic 3053, Australia; 12.Erasmus MC, Dept Neurol, NL-3000 Rotterdam, Netherlands; 13.Tech Univ Munchen Weihenstephan, Chair Dev Genet, D-85764 Neuherberg, Germany; 14.Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany; 15.Philipps Univ, Ctr Tumor Biol & Immunol, Inst Mol Biol & Tumor Res, D-35043 Marburg, Germany |
推荐引用方式 GB/T 7714 | Weber, Axel,Schwarz, Sigrid C.,Tost, Jorg,et al. Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Weber, Axel.,Schwarz, Sigrid C..,Tost, Jorg.,Truembach, Dietrich.,Winter, Pia.,...&Mueller, Ulrich.(2018).Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1.NATURE COMMUNICATIONS,9. |
MLA | Weber, Axel,et al."Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1".NATURE COMMUNICATIONS 9(2018). |
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