Résumés disponibles (91) :

HUIN Vincent (INSERM U1172 éq. 01 - Bernard SABLONNIERE)
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@mail :  vincent.huin@inserm.fr      tél. :  0320622075


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Titre de la communication :
Epigenomic variations of MAPT gene in Tauopathies
Auteurs (et leurs adresses) de la communication :
Vincent Huin1,2, Amélie Labudeck1, Vincent Deramecourt1,2, Valérie Buée1, Luc Buée1, Claire-Marie Dhaenens1,2 & Bernard Sablonnière1,2 1. UDSL, Jean-Pierre Aubert Research Center, Inserm UMR837, 59045 Lille, France 2. CHRU Lille, 59000 Lille, France
Résumé de la communication :
Epigenetics concerns heritable changes in gene function, which takes place without any alteration in the DNA sequence. It consists in histones posttranscriptionnal modifications and in reversible modifications of the DNA as cytosines methylation. There are evidences for the role of epigenetics in the pathogenesis of neurodegenerative diseases. For example, studies of monozygous twins have shown a decrease in DNA methylation in neurons of the temporal cortex in the twin suffering from Alzheimer's disease (AD). High plasma levels of homocysteine and low levels of vitamins B9 and B12 in AD patients have been observed, suggesting a deregulation of methyl donor metabolic cycles in DNA methylation. Among the different neurodegenerative diseases, tauopathies are characterized by the accumulation of abnormally and hyperphosphorylated Tau protein. In these diseases, the regulation of MAPT, the Tau coding gene, is altered with variations in gene expression and/or in the splicing. These differences have allowed definition of different classes of tauopathies according to the aggregation of different Tau isoforms.
The aim of our study is to determine whether epigenetic control of MAPT gene contributes to the expression of Tau protein. Cytosine methylation level in MAPT was assessed in brain autopsies from 43 patients with tauopathy and compared to 11 controls. Frontal and occipital areas are selected. 6 candidate regions, including methylated sites, CpG islands, post-transcriptionnal histone modifications, transcription factors or CTCF binding sites were investigated. Pyrosequencing analysis revealed variations in methylation levels in one MAPT intron -1 CpG for PSP and Pick patients versus controls. To evaluate the implication of methylation in differential expression of transcripts between these 2 tauopathy classes, MAPT total and transcripts expression was assessed by qPCR. Results suggest that an alternative promoter could be up-regulated in pathological conditions, under methylation control, and could be responsible for specific Tau transcipts expression. In vitro studies will be necessary to confirm the direct link between methylation and alternative promoter regulation.

HUIN Vincent (INSERM U1172 éq. 01 - Bernard SABLONNIERE)