title: TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells.
abstract: 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 Translocation (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.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Rome, Italy; Pasteur Institute - Cenci Bolognetti Foundation of Rome, "Sapienza" University of Rome, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Calabrese
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Rome, Italy; Pasteur Institute - Cenci Bolognetti Foundation of Rome, "Sapienza" University of Rome, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Valentini
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Rome, Italy; Pasteur Institute - Cenci Bolognetti Foundation of Rome, "Sapienza" University of Rome, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ciccarone
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Rome, Italy; Pasteur Institute - Cenci Bolognetti Foundation of Rome, "Sapienza" University of Rome, Rome, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Guastafierro
authors.affiliation: Department of Experimental Pathology, University of Bologna, Bologna, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Bacalini
authors.affiliation: Center for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy; Neuroimmunology Unit, Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
authors.forename: V A G
authors.initials: VA
authors.lastname: Ricigliano
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Rome, Italy; Pasteur Institute - Cenci Bolognetti Foundation of Rome, "Sapienza" University of Rome, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zampieri
authors.affiliation: Center for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Annibali
authors.affiliation: Center for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Mechelli
authors.affiliation: Department of Experimental Pathology, University of Bologna, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Center for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy. Electronic address: marco.salvetti@uniroma1.it.
authors.forename: M
authors.initials: M
authors.lastname: Salvetti
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Rome, Italy; Pasteur Institute - Cenci Bolognetti Foundation of Rome, "Sapienza" University of Rome, Rome, Italy. Electronic address: caiafa@bce.uniroma1.it.
authors.forename: P
authors.initials: P
authors.lastname: Caiafa
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000328:Adult; D016022:Case-Control Studies; D003596:Cytosine / Q000031:analogs & derivatives* / Q000097:blood; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D049308:Dioxygenases; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D049308:Dioxygenases; C541081:TET2 protein, human; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human
keywords: 5-Hydroxymethylcytosine; DNA methylation; Epigenetics; Multiple sclerosis; Peripheral blood mononuclear cells; Ten-Eleven Translocation 2