Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/30/2007
Publication Date: 5/30/2007
Citation: Li, C.-J, Elsasser, T.H., Li, R.W. 2007. Epigenetic mechanisms at work: Exploiting nutrient-specific modulation of genetic networks [abstract]. 29th General Assembly of the International Union of Biological Sciences and Scientific Symposium. Proceedings p7, Washington, DC.
Technical Abstract: “Epigenetics” was used to describe actions of genes with their environment that bring the phenotype into being”. The modern version of epigenetics includes the molecular mechanisms that influence the phenotypic outcome of a gene or genome, in absence of changes to the underlying DNA sequence. A host of genomic interrelationships with the diet evidently exist. These encompass the broad topic of nutrigenomics as defined with respect to the interaction between nutrition and an individual's genome. The presented study, using genomics and molecular techniques, bioinformatics and computation, as well as knowledge integration, reveals that the short-chain volatile fatty acids (VFA, acetate, propionate, and butyrate), especially butyrate, are involved in metabolism not only as nutrient, but also as genomic regulator. The detailed mechanisms by which butyrate induces cell growth arrest and apoptosis were analyzed using global gene expression profiles and the Ingenuity Pathways Knowledge Base. Gene expression profiling with high-density oligonucleotide microarrays indicated that butyrate induces many significant changes in the expression of genes associated with many regulatory pathways that are critical to cell growth, immune response and signal transduction. The functional category and pathway analyses of the microarray data revealed that several canonical pathways (Cell cycle: G2/M DNA damage checkpoint; pyrimidine metabolism; Cell cycle: G1/S Checkpoint Regulation; and purine metabolism; insulin-like growth factor axis components) were significantly affected. The present findings provide an example of epigenetic regulation of genome at work and basis for understanding the full range of the biological roles and the molecular mechanisms that butyrate may play in human and animal cell growth, proliferation, and energy metabolism. The results illustrate the potential to exploit nutritional manipulation of gene activity for health maintenance in a drug residue-free format and further suggest that the outcomes of manipulation may be modulated in concert with controlled stages of the cell cycle.