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Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency
- Publication Year :
- 2011
- Publisher :
- ELSEVIER SCIENCE INC, 2011.
-
Abstract
- We have previously shown that a nutritional model of B vitamin deficiency and homocysteine cycle alteration could lead to increased amyloid β 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.
- Subjects :
- Aging
Hyperhomocysteinemia
Mice, Transgenic
dna methylation
s-adenosylmethionine
Biology
Transfection
b vitamins
epigenetic
homocysteine
presenilin 1
Amyloid beta-Protein Precursor
Mice
Vitamin B Deficiency
Cell Line, Tumor
Presenilin-1
medicine
Animals
Humans
Sulfites
RNA, Messenger
Epigenetics
Promoter Regions, Genetic
Regulation of gene expression
Analysis of Variance
General Neuroscience
Brain
Sequence Analysis, DNA
Methylation
medicine.disease
Molecular biology
Disease Models, Animal
B vitamins
Gene Expression Regulation
CpG site
Mutation
DNA methylation
Cancer research
Neurology (clinical)
Geriatrics and Gerontology
Developmental Biology
DNA hypomethylation
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....36bec5f60e0622372d9edb495fd7fa9b