Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/30/2009
Publication Date: N/A
Technical Abstract: 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. One paradigmatic example of the 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 that are induced by VFA. Our recent studies indicate that VFA also induces 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 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.