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

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

Research output: Contribution to journal › Article

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.

Original language	English
Pages (from-to)	1130-1136
Number of pages	7
Journal	Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume	1842
Issue number	7
DOIs	https://doi.org/10.1016/j.bbadis.2014.04.010
Publication status	Published - 2014

Keywords

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

ASJC Scopus subject areas

Molecular Biology
Molecular Medicine

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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. (2014). TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1842(7), 1130-1136. https://doi.org/10.1016/j.bbadis.2014.04.010

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

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1842, No. 7, 2014, p. 1130-1136.

Research output: Contribution to journal › Article

Calabrese, R, Valentini, E, Ciccarone, F, Guastafierro, T, Bacalini, MG, Ricigliano, VAG, Zampieri, M, Annibali, V, Mechelli, R, Franceschi, C, Salvetti, M & Caiafa, P 2014, 'TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1842, no. 7, pp. 1130-1136. https://doi.org/10.1016/j.bbadis.2014.04.010

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. / TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2014 ; Vol. 1842, No. 7. pp. 1130-1136.

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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.",

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AU - Caiafa, P.

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