We have previously shown that a nutritional model of B vitamin deficiency and homocysteine cycle alteration could lead to increased amyloid beta deposition, due to PSEN 1 and BACE over-expression and consequent increase in secretase activity. We hypothesize that nutritional factors causing homocysteine cycle alterations (i.e. hyperhomocysteinemia) could induce sequence-specific DNA hypomethylation and "aberrant" gene activation. Aim of present study was to analyze the methylation pattern of PSEN 1 promoter in SK-N-BE neuroblastoma cells and TgCRND8 mice, in a B vitamin (folate, B12 and B6) deficiency paradigm. PSEN 1 methylation status has been evaluated through bisulphite modification and genomic sequencing. We demonstrate that B vitamin deficiency induces hypomethylation of specific CpG moieties in the 5'-flanking region; S-adenosylmethionine has been supplemented as methyl donor to reverse this effect. PSEN 1 promoter methylation status is correlated with gene expression. These findings pinpoint a direct relationship between B vitamin-dependent alteration of homocysteine cycle and DNA methylation and also indicate that PSEN 1 promoter is regulated by methylation of specific CpG moieties. (C) 2009 Elsevier Inc. All rights reserved.

Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency / Fuso, Andrea; Nicolia, Vincenzina; Alessia, Pasqualato; Fiorenza, Maria Teresa; Cavallaro, ROSARIA ADELE; Scarpa, Sigfrido. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - STAMPA. - 32:2(2011), pp. 187-199. [10.1016/j.neurobiolaging.2009.02.013]

Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency

FUSO, ANDREA;NICOLIA, Vincenzina;FIORENZA, Maria Teresa;CAVALLARO, ROSARIA ADELE;SCARPA, Sigfrido
2011

Abstract

We have previously shown that a nutritional model of B vitamin deficiency and homocysteine cycle alteration could lead to increased amyloid beta deposition, due to PSEN 1 and BACE over-expression and consequent increase in secretase activity. We hypothesize that nutritional factors causing homocysteine cycle alterations (i.e. hyperhomocysteinemia) could induce sequence-specific DNA hypomethylation and "aberrant" gene activation. Aim of present study was to analyze the methylation pattern of PSEN 1 promoter in SK-N-BE neuroblastoma cells and TgCRND8 mice, in a B vitamin (folate, B12 and B6) deficiency paradigm. PSEN 1 methylation status has been evaluated through bisulphite modification and genomic sequencing. We demonstrate that B vitamin deficiency induces hypomethylation of specific CpG moieties in the 5'-flanking region; S-adenosylmethionine has been supplemented as methyl donor to reverse this effect. PSEN 1 promoter methylation status is correlated with gene expression. These findings pinpoint a direct relationship between B vitamin-dependent alteration of homocysteine cycle and DNA methylation and also indicate that PSEN 1 promoter is regulated by methylation of specific CpG moieties. (C) 2009 Elsevier Inc. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/228027
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