Role of DNA methylation in the dietary restriction mediated cellular memory

Dietary restriction (DR) appears to create a cellular memory, which persists even after DR is discontinued.DNA methylation seems a logical mechanism by which a cellular memory could be established.we first examined the effect of short-term DR on gene expression and DNA methylation, then determined whether the changes persisted after DR was discontinued and mice returned to ad libitum (AL) feeding.We show that DR can induce substantial changes in gene expression within one month of its implementation in various tissues, and ~15-50% of these changes in gene expression persist even when DR is discontinued. We then determined whether DR induced changes in DNA methylation in the promoter of three candidate genes (Pomc, Hsph1 and Nts1) that were correlated with the changes in the expression of these genes. mRNA profiles in 5 tissues (Liver, Epididymal fat, Colon, Hypothalamus, Hippocampus) of mice under three feeding diets (ad libitum (AL), diet restricted, ad libitum after diet restricted)