ARS | Publication request: ROLES OF NUTRIENTS IN EPIGENTIC EVENTS CAN BE CHARACTERIZED BY USING A COMBINATION OF CHROMATIN IMMUNOPRECIPITATION ASSAYS AND DNA MICROARRAYS

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 27, 2004
Publication Date: February 1, 2005
Citation: Oommen, A.M., Griffin, J.B., Sarath, G., Zempleni, J. 2005. Roles of nutrients in epigentic events can be characterized by using a combination of chromatin immunoprecipitation assays and dna microarrays. Journal of Nutritional Biochemistry.(2005). 16:74-77.

Interpretive Summary: Each cell of a multicellular organism contains an identical sequence and amount of DNA. The DNA of higher organisms is packaged within a specialized compartment termed the nucleus. DNA is assembled with a number of DNA-binding proteins into long strands called chromatin. Chromatin is packaged into larger structures called chromosomes. In order to function, DNA packaged into chromatin must become accessible to the cellular biosynthetic machinery so that appropriate regulation of genes can occur. This interplay between the nucleus and the rest of the cell in response to biotic and abiotic cues determines the developmental fate of a particular cell. The study of DNA and how it is passed on through generations (heredity) is called 'genetics'. In contrast, the field of epigenetics is the study of modifications of DNA and DNA-binding proteins that alter the structure of chromatin without altering the nucleotide sequence of DNA; some of these modifications may be associated with heritable changes in gene function. Epigenetic modifications and control mechanisms are critical to the well-being of a cell; miscues in these processes can lead to diseased states. It is known that vitamins play essential roles in epigenetic events. In order to decipher how vitamins influence epigenetic events and to ascertain the nature of vitamin-induced modifications to DNA and DNA-binding proteins, we present a novel procedure to map nutrient-dependent epigenetic marks in the entire genomes of any given species: this involves the combined use of chromatin immunoprecipitation assays and DNA microarrays. This procedure also is an excellent tool to map the enzymes that mediate modifications of DNA and DNA-binding proteins in chromatin. Given the tremendous opportunities offered by the combined use of chromatin immunoprecipitation assays and DNA microarrays, we can expect seeing a surge of information related to roles for nutrients in epigenetic events.

Technical Abstract: The field of epigenetics is the study of modifications of DNA and DNA-binding proteins that alter the structure of chromatin without altering the nucleotide sequence of DNA; some of these modifications may be associated with heritable changes in gene function. Nutrients play essential roles in the following epigenetic events. First, folate participates in the generation of S-adenosylmethionine, which acts as a methyl donor in the methylation of cytosines in DNA; methylation of cytosines is associated with gene silencing. Second, covalent attachment of biotin to histones (DNA-binding proteins) plays a role in gene silencing and the cellular response to DNA damage. Third, tryptophan and niacin are converted to NAD, which is a substrate for poly(ADP-ribosylation) of histones and other DNA-binding proteins; poly(ADP-ribosylation) of these proteins participates in DNA repair and apoptosis. Here we present a novel procedure to map nutrient-dependent epigenetic marks in the entire genomes of any given species: the combined use of chromatin immunoprecipitation assays and DNA microarrays. This procedure also is an excellent tool to map the enzymes that mediate modifications of DNA and DNA-binding proteins in chromatin. Given the tremendous opportunities offered by the combined use of chromatin immunoprecipitation assays and DNA microarrays, the nutrition community can expect seeing a surge of information related to roles for nutrients in epigenetic events.