TY - JOUR
T1 - TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells
AU - Calabrese, R.
AU - Valentini, E.
AU - Ciccarone, F.
AU - Guastafierro, T.
AU - Bacalini, M. G.
AU - Ricigliano, V. A G
AU - Zampieri, M.
AU - Annibali, V.
AU - Mechelli, R.
AU - Franceschi, C.
AU - Salvetti, M.
AU - Caiafa, P.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - 5-Hydroxymethylcytosine
KW - DNA methylation
KW - Epigenetics
KW - Multiple sclerosis
KW - Peripheral blood mononuclear cells
KW - Ten-Eleven Translocation 2
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UR - http://www.scopus.com/inward/citedby.url?scp=84899848583&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2014.04.010
DO - 10.1016/j.bbadis.2014.04.010
M3 - Article
C2 - 24735979
AN - SCOPUS:84899848583
VL - 1842
SP - 1130
EP - 1136
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 7
ER -