Send Orders of Reprints at reprints@benthamscience.net The Open Nutraceuticals Journal, 2013, 6, 27-34 27 1876-3960/13 2013 Bentham Open Open Access Effect of Diet and Nutrients on Molecular Mechanism of Gene Expression Mediated by Nuclear Receptor and Epigenetic Modulation Mahsa Jalili 1,* , Sanghamitra Pati 2 , Bandita Rath 3 , Geir Bjørklund 4 and Ram B. Singh 5 1 Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Public Health Foundation of India (PHFI), Indian Institute of Public Health, Bhubaneswar, Odisha, India 3 Guest Faculty, Utkal University, Bhubaneswar, Odisha, India 4 Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway 5 Halberg Hospital and Research Institute, Moradabad, India 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. Keywords: Diet, nutrition, epigenetic changes, gene expression, transcription, nuclear receptors. 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 *Address correspondence to this author at the Nutrition Faculty, Students Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Tel: 0098 212387; E-mail: jalili.mah@gmail.com through several different transcriptional signal cascades and networks, despite still insufficient knowledge about all cellu- lar mechanisms that mediate these effects. The body needs a prudent diet composition to be healthy without premature development of NCDs. The diet provides nutrients to various body systems that are needed for normal metabolism and optimal physiological functions, including intestinal func- tion, cellular growth and DNA repair. The amount and qual- ity of food has dramatic effects on processes at a molecular level in the cells. Epigenetics is the science that aims to study quasi- heritable, but reversible changes in gene function. There is no change in the nucleotide sequence of the DNA molecules; however, gene function is not only determined by the DNA sequence and code, but also by epigenetic phenomena. Re- cent evidence has provided further proof that environmental factors, including diet and nutrients, can influence cell- signaling pathways that control normal physiological growth as well as the growth of cancer cells by directly influencing gene expression. Epigenetic mechanisms are important de- terminants for activation or repression of gene expression