TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells

R Calabrese (1, 2) , E Valentini (1, 2) , F Ciccarone (1, 2) , T Guastafierro (1, 2) , Maria G Bacalini (3) , V.A.G. Ricigliano (4, 5) , M Zampieri (1, 2) , V Annibali (4) , R Mechelli (4) , C Franceschi (3) , M Salvetti (4) , P Caiafa (1, 2)

1 Department of Cellular Biotechnologies and Hematology
2 Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti
3 Department of Experimental Pathology
4 Center for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs
5 Neuroimmunology Unit

Aberrant DNA methylation can lead to genome destabilization and to deregulated gene expression. Recently, 5-hydroxymethylcytosine (5hmC), derived from oxidation of 5-methylcytosine (5mC) by the Ten-Eleven Translo-cation (TET) enzymes, has been detected. 5hmC is now considered as a new epigenetic DNA modification with relevant roles in cell homeostasis regulating DNA demethylation and transcription. Our aim was to investigate possible changes in the DNA methylation/demethylation machinery in MS. We assessed the expression of enzymes involved in DNA methylation/demethylation in peripheral blood mononuclear cells (PBMCs) from 40 subjects with MS and 40 matched healthy controls. We performed also, DNA methylation analysis of specific promoters and analysis of global levels of 5mC and 5hmC. We show that TET2 and DNMT1 expression is significantly down-regulated in MS PBMCs and it is associated with aberrant methylation of their promoters. Furthermore , 5hmC is decreased in MS PBMCs, probably as a result of the diminished TET2 level.

Mots clés: 5-Hydroxymethylcytosine; DNA methylation; Epigenetics; Multiple sclerosis; Peripheral blood mononuclear cells; Ten-Eleven Translocation 2

Domaines: Biochimie, Biologie Moléculaire; Biologie cellulaire

R Calabrese, E Valentini, F Ciccarone, T Guastafierro, Maria G Bacalini, et al.. TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells. BBA - Biochimica et Biophysica Acta, 2014, 1842 (7), pp.1130-6. ⟨10.1016/j.bbadis.2014.04.010⟩. ⟨pasteur-01163745⟩