Aberrant DNA methylation can lead to genome destabilization and to deregulated gene expression. Recently, 5- hydroxymethylcytosine (5hmC), derived fromoxidation 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 inDNA methylation/demethylation in peripheral blood mononuclear cells (PBMCs) from40 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
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. (C) 2014 Elsevier B.V. All rights reserved.
TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells / Calabrese, Roberta; Valentini, Elisabetta; Ciccarone, Fabio; Guastafierro, Tiziana; Bacalini, MARIA GIULIA; Ricigliano, VITO ANTONIO GERARDO; Zampieri, Michele; Annibali, Viviana; Mechelli, Rosella; C., Franceschi; Salvetti, Marco; Caiafa, Paola. - In: BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE. - ISSN 0925-4439. - ELETTRONICO. - 1842:7(2014), pp. 1130-1136. [10.1016/j.bbadis.2014.04.010]
TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells
CALABRESE, ROBERTA;VALENTINI, ELISABETTA;CICCARONE, FABIO;GUASTAFIERRO, Tiziana;BACALINI, MARIA GIULIA;RICIGLIANO, VITO ANTONIO GERARDO;ZAMPIERI, Michele;ANNIBALI, Viviana;MECHELLI, Rosella;SALVETTI, Marco;CAIAFA, Paola
2014
Abstract
Aberrant DNA methylation can lead to genome destabilization and to deregulated gene expression. Recently, 5- hydroxymethylcytosine (5hmC), derived fromoxidation 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 inDNA methylation/demethylation in peripheral blood mononuclear cells (PBMCs) from40 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 aI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
