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Journal articles
Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1
Axel Weber
1
Sigrid Schwarz
2, 3
Jorg Tost
4, 5
Dietrich Trümbach
6, 7
Pia Winter
1
Florence Busato
5, 4
Pawel Tacik
8
Anita Windhorst
1
Maud Fagny
4, 5
Thomas Arzberger
3
Catriona Mclean
9
John van Swieten
10
Johannes Schwarz
2
Daniela Vogt Weisenhorn
3, 7
Wolfgang Wurst
3, 7
Till Adhikary
11
Dennis Dickson
8
Günter Höglinger
2, 3
Ulrich Müller
1
Axel Weber 1
Author
Sigrid C. Schwarz 2, 3
Author
Jorg Tost 4, 5
Author
Dietrich Trümbach 6, 7
Author
Maud Fagny 4, 5
Author
Thomas Arzberger 3
Author
Catriona Mclean 9
Author
John van Swieten 10
Author
Johannes Schwarz 2
Author
Daniela Vogt Weisenhorn 3, 7
Author
Wolfgang Wurst 3, 7
Author
Till Adhikary 11
Author
1
JLU - Justus-Liebig-Universität Gießen (Ludwigstraße 23, 35390 Gießen - Germany)
2
TUM - Technische Universität München [München] (Arcisstraße 21, 80333 München - Germany)
3
DZNE - University of Munich (France)
4
CNG - Centre National de Génotypage (Centre National de Génotypage 2 rue Gaston Crémieux CP5721 91057 EVRY Cedex - France)
- CEA - Commissariat à l'énergie atomique et aux énergies alternatives : DSV/IG (Centre de Saclay Centre de Grenoble Centre de Cadarache etc - France)
5
JACOB - Institut de Biologie François JACOB (DRF
CEA
Fontenay-aux-Roses - France)
- DRF (CEA) - Direction de Recherche Fondamentale (CEA) : DRF/JACOB (Direction de Recherche Fondamentale
Fundamental Research Division
CEA Saclay
91191 Gif-sur-Yvette
- France)
- CEA - Commissariat à l'énergie atomique et aux énergies alternatives (Centre de Saclay Centre de Grenoble Centre de Cadarache etc - France)
7
Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Lehrstuhl für Entwicklungsgenetik, (Ingolstädter Landstrasse 1, D-85764 Neuherberg - Germany)
- TUM - Technische Universität München [München] (Arcisstraße 21, 80333 München - Germany)
8
Mayo Clinic [Jacksonville] (4500 San Pablo Road Jacksonville, FL 32224 - United States)
9
State Neuropathology Service, Department of Pathology (Melbourne - Australia)
- University of Melbourne (Parkville VIC 3010 - Australia)
10
Erasmus MC - Erasmus University Medical Center [Rotterdam] (Rotterdam - Netherlands)
11
Philipps Universität Marburg (Philipps-Universität Marburg, Biegenstraße 10, 35032 Marburg - Germany)
Abstract : 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
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Journal articles
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https://hal-cea.archives-ouvertes.fr/cea-01877684
Contributor : Bruno Savelli <>
Submitted on : Thursday, September 20, 2018 - 11:18:29 AM
Last modification on : Monday, May 18, 2020 - 12:24:06 PM
Contributor : Bruno Savelli <>
Submitted on : Thursday, September 20, 2018 - 11:18:29 AM
Last modification on : Monday, May 18, 2020 - 12:24:06 PM
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- HAL Id : cea-01877684, version 1
- DOI : 10.1038/s41467-018-05325-y
Citation
Axel Weber, Sigrid Schwarz, Jorg Tost, Dietrich Trümbach, Pia Winter, et al.. Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1. Nature Communications, Nature Publishing Group, 2018, 9, pp.2929. ⟨10.1038/s41467-018-05325-y⟩. ⟨cea-01877684⟩
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