Effect Of Diet and Nutrients on Molecular Mechanism of Gene Expression Mediated By Nuclear Receptor and Epigenetic Modulation

Abstract

Major research progress in the last few decades has elucidated the complex nexus between nutrition and health. Diet and lifestyle influence epigenetic changes that are heritable. However, a statement of reservation is needed here, viz. that it is often difficult to distinguish between epigenetic changes that are inherited from one generation to the next and true mutations, for instance in mitochondrial DNA. The last topic is a big one in its own right and will not be further dis-cussed in this article. Epigenetic changes induced by dietary nutrients ultimately culminate in changes of the expression of genes through transcription and translation. The interaction between dietary nutrients and nuclear receptors triggers the signaling pathway, leading to modulation of epigenetic change and gene expression. Knowledge about nuclear receptors is important for explaining dietary modulation of transcription via recruitment of large protein complexes. These proteins are capable of causing modification of chromosomal components, can influence chromatin proteins, and affect the binding of proteins to particular parts of the DNA molecules controlling the expression of individual genes. Chromatin complexes between DNA and proteins can be destabilized by recruitment of transcriptional coactivators by histone acetylation. How-ever, in the presence of hormone antagonists or in the absence of relevant ligands, recruitment of other cellular core pro-teins may stabilize chromatin by their influence on histone deacetylases, thus antagonizing the effect of enzymes causing histone acetylation. This article reviews the current knowledge on nutritional modulation of bioactive molecules by epige-netic changes, if they can regulate genetic expressions. The molecular mechanism of action of various dietary nutrients on gene expression mediated by nuclear receptors is also discussed. INTRODUCTION Dietary and lifestyle factors can interact with genes and may have a negative impact of health that can predispose for the development of non-communicable diseases (NCDs), such as cardiovascular diseases (CVDs), type 2 diabetes and cancer, for which prevention is a global priority, while other nutrients and lifestyle factors can have an opposite, protec-tive effect [1, 2]. Recent studies conducted in the last few decades have emphasized the role of nutrition in health and prevention of NCDs. Nutrients that are available extracellu-larly are important determinants of eukaryotic cell growth and growth of the whole organism, since several different nutrient deficiencies can lead to inhibition or serious distur-bance of growth and development at both levels. It is well established that nutrients can influence the expression of genes controlling metabolic processes via signal transduction