Epigenetic regulation of gene expression and cellular functions induced by butyrate, an example of interactions between gene and nutrients

Authors: Li, Congjun - Cj; Li, Robert; Elsasser, Theodore; Connor, Erin

Submitted to: American Dairy Science Association Discover Conference
Publication Type: Abstract Only
Publication Acceptance Date: 10/28/2009
Publication Date: 11/2/2009
Citation: Li, C., Li, R.W., Elsasser, T.H., Connor, E.E. 2009. Epigenetic regulation of gene expression and cellular functions induced by butyrate, an example of interactions between gene and nutrients. American Dairy Science Association Discover Conference.

Interpretive Summary:

Technical Abstract: Epigenetics has been defined as ‘the study of heritable changes in genome function that occur without a change in DNA sequence. Research on nutrigenomics, the genome-nutrient interface and epigenomics is in its infancy with respect to livestock species. Feed costs are the single greatest expense to dairy and beef production and are estimated to account for approximately 50% of production costs. Inefficiency of nutrient uptake and use by the animal can also contribute to economic losses resulting from lowered production, decreased fertility and longevity, and compromised immune function. Volatile short-chain fatty acids (VFAs, acetate, propionate, and butyrate) are nutrients especially critical to ruminants, and are formed during microbial fermentation of dietary fiber in the gastrointestinal tract and are directly absorbed at the site of production Volatile fatty acids (VFA), especially butyrate, participate in metabolism both as nutrients and as regulators of histone deacetylation. The major biochemical change that occurs in cells treated with butyrate is the global hyperacetylation of histones, which is also one of the major epigenetic regulators. One paradigmatic example of nutrient-epigenetic-phenotype relationship is that of VFA and their gene expression regulation activities. Utilizing gene expression profiling, our studies indicated that butyrate induces many significant changes in the expression of genes associated with regulatory pathways that are critical to cell growth, immune response and signal transduction. We identified 450 genes significantly regulated by sodium butyrate at a very stringent false discovery rate (FDR) = 0%. The functional category and pathway analyses of the microarray data revealed that 4 canonical pathways (Cell cycles checkpoint; pyrimidine metabolism; G1/S checkpoint regulation and purine metabolism) were significantly perturbed. The biologically relevant networks and pathways of these genes were also identified. IGF2, TGFB1, TP53, E2F4, and CDC2 were established as being centered in these genomic networks. The profound changes in gene expression induced by butyrate in bovine cells elucidate the pleiotropic effects of histone acetylation. However, histone acetylation is not the only epigenetic mechanisms induced by VFA. Our recent studies indicate that VFA also induce reactivation of the somatically heritable imprint genes such as IGF2 (loss of imprinting). miRNA, a group of non-coding short RNAs, is also involved in butyrate-induced epigenetic regulation of gene expression. Butyrate induced biological effects in bovine cells provide an example of epigenetic regulation of the genome and a basis for understanding the full range of biological roles and molecular mechanisms that butyrate may play in animal cell growth, proliferation, and energy metabolism.