Nutrients, epigenetics, and cancer disease

Epigenetic phenomena transmit non-coded information in DNA sequence from cell to daughter cell or from generation to generation through mitosis. Cytosine methylation of DNA and modification of DNA packaging proteins, histones, are the main epigenetic phenomena. DNA methylation within genes or gene regulatory elements such as exons and promoters generally suppresses transcription of the gene, while methylation within gene deficient regions, such as heterochromatin, appears crucial for maintaining the conformation and integrity of the chromosome. DNA methylation also plays an important role in genomic imprinting and transcriptional silencing of transposons. DNA exists in the context of chromatin: segments of DNA wrapped around a nucleosome that is composed of 2 molecules each of histones H2A, H2B, H3, and H4. Tails of these histones are modified by acetylation, methylation, phosphorylation, and ubiquitination, interactions of which determine the accessibility of DNA methyltransferases, methyl-CpG binding proteins, chromatin-remodelling proteins, and transcription factors. Methylation of the mammalian genome undergoes dramatic changes during early development and appears to be an integral mechanism for the rapid differentiation and formation of various tissues and organs. As differentiation approaches completion, the methylation pattern displays tissue-specificity and established patterns are stably maintained during later life. However, these patterns are not immutable and can be affected by nutritional status. Nutrients, which can affect one-carbon metabolism, such as methionine, choline, betaine, folate, vitamin B12, vitamin B6, riboflavin, zinc and selenium, can alter the methylation status of DNA and histones by impinging on cellular levels of S-adenosylmethionine and S-adenosylhomocysteine. Nutrients such as butyrate and sulforaphane also can affect histone acetylation status by inhibiting histone deacetylases. Since DNA methylation and histone modification are now regarded as candidate mechanisms for carcinogenesis, we anticipate that nutritional modulation of one-carbon metabolism or histone modifying enzymes might prevent carcinogenesis. Collectively, nutrients are important for the epigenetic control of gene expression and integrity. Future studies regarding the nutritional modulation of epigenetics will enable us to understand the molecular mechanisms of epigenetics as well as to facilitate to find new cancer preventive or therapeutic modalities.