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
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.
Department of Experimental Pathology, University of Bologna, Bologna, Italy.
Biochim Biophys Acta. 2014 Jul;1842(7):1130-6. doi: 10.1016/j.bbadis.2014.04.010. Epub 2014 Apr 13.
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.
异常的DNA甲基化可导致基因组不稳定和基因表达失调。最近，已检测到由十一转位（TET）酶将5-甲基胞嘧啶（5mC）氧化产生的5-羟甲基胞嘧啶（5hmC）。5hmC现在被认为是一种新的表观遗传DNA修饰，在调节DNA去甲基化和转录的细胞稳态中具有相关作用。我们的目的是研究多发性硬化症（MS）中DNA甲基化/去甲基化机制的可能变化。我们评估了40例MS患者和40例匹配的健康对照者外周血单个核细胞（PBMC）中参与DNA甲基化/去甲基化的酶的表达。我们还进行了特定启动子的DNA甲基化分析以及5mC和5hmC整体水平的分析。我们发现，TET2和DNMT1在MS患者PBMC中的表达显著下调，并且这与它们启动子的异常甲基化有关。此外，MS患者PBMC中的5hmC减少，这可能是TET2水平降低的结果。
