A growing body of literature suggests that Multiple Sclerosis (MS) holds an epigenetic component that mediates the effects of common environmental risk factors on disease progression. Some of the major epigenetic modifications on DNA are the addition of a methyl or a hydroxymethyl group to the C5 cytosine position, leading to 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) formation. Interestingly, several neurodegenerative disorders have been associated to abnormal epigenetic modifications patterns, as observed with the global DNA methylation loss in MS white matter. Indeed, the abnormal expression of DNA methylation/hydroxymethylation enzymes is well documented in several other conditions, such as Alzheimer's disease and cancer. This project links the DNA methylation instability in MS white matter to the altered expression of DNA methylation/hydroxymethylation enzymes. Our preliminary observations indicate that MS normal appearing white matter shows a global 5hmC reduction, as well as a decrease of its successive oxidation products 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). These epigenetic changes are also associated with TET2 and IDAX gene expression alterations. Results from this study would form the basis for future investigations aimed at establishing if these changes are linked to DNA epigenetic patterns alteration in MS, thus paving the way for innovative disease treatments through “epigenetic” drugs.
Link between 5-hydroxymethycytosine levels and TET enzymes transcription in human MS brain / Tagliatesta, S; Ciccarone, F; Aversano, V; Novara, L; Nocchia, D; Reale, A; Salvetti, M; Caiafa, P; Zampieri, M. - (2017). (Intervento presentato al convegno The Biennial Congress of the Italian Association of Cell Biology and Differentiation tenutosi a Bologna, Italy).
Link between 5-hydroxymethycytosine levels and TET enzymes transcription in human MS brain
Tagliatesta S;Ciccarone F;Nocchia D;Reale A;Salvetti M;Caiafa P;Zampieri M
2017
Abstract
A growing body of literature suggests that Multiple Sclerosis (MS) holds an epigenetic component that mediates the effects of common environmental risk factors on disease progression. Some of the major epigenetic modifications on DNA are the addition of a methyl or a hydroxymethyl group to the C5 cytosine position, leading to 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) formation. Interestingly, several neurodegenerative disorders have been associated to abnormal epigenetic modifications patterns, as observed with the global DNA methylation loss in MS white matter. Indeed, the abnormal expression of DNA methylation/hydroxymethylation enzymes is well documented in several other conditions, such as Alzheimer's disease and cancer. This project links the DNA methylation instability in MS white matter to the altered expression of DNA methylation/hydroxymethylation enzymes. Our preliminary observations indicate that MS normal appearing white matter shows a global 5hmC reduction, as well as a decrease of its successive oxidation products 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). These epigenetic changes are also associated with TET2 and IDAX gene expression alterations. Results from this study would form the basis for future investigations aimed at establishing if these changes are linked to DNA epigenetic patterns alteration in MS, thus paving the way for innovative disease treatments through “epigenetic” drugs.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.