title: The MAPT gene is differentially methylated in the progressive supranuclear palsy brain.
abstract: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease causing parkinsonian symptoms. Altered DNA methylation of the microtubule-associated protein tau gene correlates with the expression changes in Alzheimer's disease and Parkinson's disease brains. However, few studies examine the sequences beyond the constitutive promoter.
  
  
  
  Because activating different microtubule-associated protein tau gene control regions via methylation might regulate the differential tau expression constituting the specific signatures of individual tauopathies, we compared methylation of a candidate promoter, intron 0.
  
  
  
  We assessed DNA methylation in the brains of patients with different tauopathies (35 Alzheimer's disease, 10 corticobasal degeneration, and 18 PSP) and 19 controls by intron 0 pyrosequencing. We also evaluated methylation in an independent cohort of 11 PSP cases and 12 controls. Frontal (affected by tau pathology) and occipital (unaffected) cortices were analyzed.
  
  
  
  In the initial samples, one CpG island site in intron 0 (CpG1) showed significant hypomethylation in PSP-affected frontal cortices when compared with controls (P = .022). Such hypomethylation was observed in replicate samples, but not in occipital cortices or other tauopathies. PSP and control samples (combining the initial and replicate samples) remained significantly different after adjustment for potential confounding factors (age, H1/H1 diplotype; P = .0005). PSP-affected tissues exhibited microtubule-associated protein tau RNA hyperexpression when compared with controls (P = .004), although no correlation with CpG1 methylation was observed.
  
  
  
  This exploratory study suggests that regions other than the constitutive promoter may be involved in microtubule-associated protein tau gene regulation in tauopathies and that intron 0 hypomethylation may be a specific epigenetic signature of PSP. These preliminary findings require confirmation. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Huin
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France.
authors.forename: Vincent
authors.identifier: 0000-0001-8201-5406
authors.initials: V
authors.lastname: Deramecourt
authors.affiliation: Centre Hospitalier de Wattrelos, Service de Neurologie, Wattrelos, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Caparros-Lefebvre
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France.
authors.forename: Claude-Alain
authors.initials: CA
authors.lastname: Maurage
authors.affiliation: Laboratoire de Neuropathologie Escourolle, AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Eniko
authors.initials: E
authors.lastname: Kovari
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1171 - CNR-MAJ, DISTALZ, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Buée-Scherrer
authors.affiliation: Univ. Lille, CHU Lille, EA 2694 - Santé publique : épidémiologie et qualité des soins, Département de Statistiques, Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Labreuche
authors.affiliation: Univ. Lille, CHU Lille, EA 2694 - Santé publique : épidémiologie et qualité des soins, Département de Statistiques, Lille, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Behal
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France.
authors.forename: Claire-Marie
authors.initials: CM
authors.lastname: Dhaenens
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Sablonnière
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism*; D014015:Tissue Banks; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: DNA methylation; PSP; epigenetic; microtubule-associated protein tau; tauopathy