Nutritional developmental epigenomics: immediate and long-lasting effects

Abstract

The phenotype of an individual is the result of complex interactions between genome, epigenome and current, past and ancestral environment leading to a lifelong remodelling of the epigenomes. The genetic information expression contained in the genome is controlled by labile chromatin-associated epigenetic marks. Epigenetic misprogramming during development is widely thought to have a persistent effect on the health of the offspring and may even be transmitted to the next generation. The epigenome serves as an interface between the environment and the genome. Dietary factors, including folate involved in C 1 metabolism, and other social and lifestyle exposures have a profound effect on many aspects of health including ageing and do so, at least partly, through interactions with the genome, which result in altered gene expression with consequences for cell function and health throughout the life course. Depending on the nature and intensity of the environmental insult, the critical spatiotemporal windows and developmental or lifelong processes involved, epigenetic alterations can lead to permanent changes in tissue and organ structure and function or to phenotypic changes that can (or cannot) be reversed using appropriate epigenetic tools. Moreover, the flexibility of epigenetic marks may make it possible for environmental, nutritional and hormonal factors or endocrine disruptors to alter, during a particular spatiotemporal window in a sex-specific manner, the sex-specific methylation or demethylation of specific CpG and/or histone modifications underlying sex-specific expression of a substantial proportion of genes. Moreover, genetic factors, the environment and stochastic events change the epigenetic landscape during the lifetime of an individual. Epigenetic alterations leading to gene expression dysregulation accumulate during ageing and are important in tumorigenesis and age-related diseases. Several encouraging trials suggest that prevention and therapy of age-and lifestyle-related diseases by individualised tailoring to optimal epigenetic diets or drugs are conceivable. However, these interventions will require intense efforts to unravel the complexity of these epigenetic, genetic and environment interactions and to evaluate their potential reversibility with minimal side effects.

Nutriepigenomics Advances into Personalized Nutrition

“…In differentiated mammalian cells, DNA methylation occurs primarily at cytosines in CG dinucleotides, so called CpG methylation, which is associated with regulation of cell specific gene expression. In contrast to DNA sequence variation, epigenetic variation is sensitive to both inherited and environmental inputs [1][2][3].…”

“…A distinguishing feature of mQTLs is that they are detected across ancestry, developmental stage and tissue type [4]. Concurrently, once epigenetic modifications are introduced they can be stable and inherited, making epigenetics a potentially important pathogenic mechanism in complex metabolic diseases [1][2][3].…”

“…Specifically, it has been demonstrated that dietary deficiency or excess of the methyl group donors needed for the cellular methylation reactions can alter epigenetic patterns, which may persist for a long period and alter gene expression causing phenotypic changes [6]. The vitamins choline, folate, B6 and B12 are cofactors essential to maintaining the one-carbon transfer cycles [1,8,9].…”

“…The epigenetic state that is set during the reprogramming stages persists at some loci for the lifetime of an individual. Evidence to support a role of epigenetics in developmental programming of disease demonstrated the impact of a suboptimal intrauterine nutritional environment on the epigenome and phenotype of the offspring [1][2][3][4][5][6].…”

“…Beginning with its influence on the genetic architecture of haploid cells that participate in the creation of a new individual and continues to influence processes responsible for fetal development, cellular respiration, apoptosis, and predisposition to metabolic disease. The epigenome provides an interface between the environment and the genome [1]. Epigenetic markers are enzyme-mediated chemical modifications of DNA and of its associated chromatin proteins.…”