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

• Published in: Biochimica et biophysica acta Vol. 1842; no. 7; pp. 1130 - 1136
• Main Authors: Calabrese, R., Valentini, E., Ciccarone, F., Guastafierro, T., Bacalini, M.G., Ricigliano, V.A.G., Zampieri, M., Annibali, V., Mechelli, R., Franceschi, C., Salvetti, M., Caiafa, P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2014; Elsevier
• Subjects: 5-Hydroxymethylcytosine; 5-Methylcytosine - analogs & derivatives; Adult; Biochemistry, Molecular Biology; Case-Control Studies; Cellular Biology; 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; Down-Regulation; Epigenetics; Female; Gene Expression; Humans; Leukocytes, Mononuclear - metabolism; Life Sciences; Male; Multiple sclerosis; Multiple Sclerosis - blood; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; Peripheral blood mononuclear cells; Promoter Regions, Genetic; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - blood; Proto-Oncogene Proteins - genetics; Ten-Eleven Translocation 2; Epigenetics; DNA methylation; Peripheral blood mononuclear cells; Multiple sclerosis; 5-Hydroxymethylcytosine; Ten-Eleven Translocation 2
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2014.04.010

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. •TET2 and DNMT1 expression is down-regulated in PBMCs of MS patients.•Down-regulation is associated with differences in DNA methylation of their promoters.•Decrease of TET2 expression corresponds to low amount of 5hmC on MS patients.