Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency.
Neurobiol Aging. 2009 Mar 27;
Authors: Fuso A, Nicolia V, Pasqualato A, Fiorenza MT, Cavallaro RA, Scarpa S
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 PSEN1 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 PSEN1 promoter in SK-N-BE neuroblastoma cells and TgCRND8 mice, in a B vitamin (folate, B12 and B6) deficiency paradigm. PSEN1 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. PSEN1 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 PSEN1 promoter is regulated by methylation of specific CpG moieties.
PMID: 19329227 [PubMed - as supplied by publisher]