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

R Calabrese; E Valentini; F Ciccarone; T Guastafierro; M G Bacalini; V A G Ricigliano; M Zampieri; V Annibali; R Mechelli; C Franceschi; M Salvetti; P Caiafa

doi:10.1016/j.bbadis.2014.04.010

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

Biochim Biophys Acta. 2014 Jul;1842(7):1130-6. doi: 10.1016/j.bbadis.2014.04.010. Epub 2014 Apr 13.

Authors

R Calabrese¹, E Valentini¹, F Ciccarone¹, T Guastafierro¹, M G Bacalini², V A G Ricigliano³, M Zampieri¹, V Annibali⁴, R Mechelli⁴, C Franceschi², M Salvetti⁵, P Caiafa⁶

Affiliations

¹ 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.
² Department of Experimental Pathology, University of Bologna, Bologna, Italy.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.

PMID: 24735979
DOI: 10.1016/j.bbadis.2014.04.010

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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

5-Methylcytosine / analogs & derivatives
Adult
Case-Control Studies
Cytosine / analogs & derivatives*
Cytosine / blood
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases / genetics
DNA (Cytosine-5-)-Methyltransferases / metabolism
DNA Methylation
DNA-Binding Proteins / biosynthesis*
DNA-Binding Proteins / blood
DNA-Binding Proteins / genetics
Dioxygenases
Down-Regulation
Female
Gene Expression
Humans
Leukocytes, Mononuclear / metabolism*
Male
Multiple Sclerosis / blood*
Multiple Sclerosis / genetics*
Multiple Sclerosis / metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins / biosynthesis*
Proto-Oncogene Proteins / blood
Proto-Oncogene Proteins / genetics

Substances

DNA-Binding Proteins
Proto-Oncogene Proteins
5-hydroxymethylcytosine
5-Methylcytosine
Cytosine
Dioxygenases
TET2 protein, human
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases
DNMT1 protein, human