Alteration of Higher Order Structure of Rat Liver Chromatin by Dietary Composition

Abstract

The higher order structure of rat liver chromatin from nuclei of animals fed stock or semi-synthetic diets for 5 days was investigated by a specific enzymatic probe, micrococcal nuclease (EC 3.1.4.7). Micrococcal nuclease digests 50% of DNA in eukaryotic chromatin into acid-soluble nucleotides while 50% of the DNA is resistant to digestion because of associated nucleoproteins. This selective digestion of DNA reflects higher orders of structure of the universal chromatin subunit, the nucleosome, found in lower eukaryotes, plants and animals. When rats were fed a commercial stock diet, 50.3% of the DNA in liver chromatin was digested by micrococcal nuclease. However, when rats were fed various semi-synthetic diets, the amount of DNA susceptible to micrococcal nuclease digestion varied as a function of diet (P less than 0.0001). Differences in the amount of DNA susceptible to micrococcal nuclease ranged from 71.4% for chromatin of rats fed a high carbohydrate/fat-free diet to 38.8% for chromatin of those fed a low carbohydrate/protein-free diet. DNA fragments generated by brief micrococcal nuclease digestion were analyzed by electrophoresis on 2.5% polyacrylamide--0.5% agarose gels. Chromatin from rats fed the high carbohydrate/fat-free diet was more rapidly digested to the monomer nucleosomin-free diet. To our knowledge, these diet-induced alterations in the higher order structure of chromatin are the first to be reported as occurring by in vivo modulation.

Could Sirt1-mediated epigenetic effects contribute to the longevity response to dietary restriction and be mimicked by other dietary interventions?

“…Diet is a particularly compelling candidate environmental exposure with large potential to influence epigenetic marking, and numerous studies provide proof of principle that diet can have epigenetic consequences. The observation that the susceptibility of rat liver chromatin to digestion by micrococcal nuclease was altered as a function of diet was an early indication of the potential of diet to modify gross chromatin structure (Castro and Sevall 1980). Intermediates in 1-carbon metabolism, specifically folate, choline, betaine and methionine, have been a focus for much of the research on effects of individual dietary components on DNA methylation.…”

Chromatin supraorganization and extensibility in mouse hepatocytes following starvation and refeeding

“…In rodent liver cells, starvation or malnutrition modifies histone H 1 and histones of the nucleosome core and can promote DNA hypomethylation and changes in the enzymatic activity of topoisomerases and helix‐destabilizing proteins (18). A generalized increase in chromatin higher‐order structure (condensation) after up to 52 h of starvation has been shown with molecular biology and topochemical assays (18–20).…”

The potential role of epigenetic responses to diet in ageing

“…Some of the earliest evidence for epigenetic effects of diet, however, is based on adult rodents; more than 30 years ago Castro and Sevall reported effects of diet on the susceptibility of rat liver chromatin to digestion by micrococcal nuclease (60) . Some of the earliest evidence for epigenetic effects of diet, however, is based on adult rodents; more than 30 years ago Castro and Sevall reported effects of diet on the susceptibility of rat liver chromatin to digestion by micrococcal nuclease (60) .…”