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Title: Epigenetic regulation in bovine cells: nutrient-induced modulation of gene expression and cellular functions

Author
item Li, Congjun - Cj
item Li, Robert
item Elsasser, Theodore

Submitted to: International Plant and Animal Genome IX Conference
Publication Type: Abstract Only
Publication Acceptance Date: 10/10/2008
Publication Date: 10/12/2008
Citation: Li, C., Li, R.W., Elsasser, T.H. 2008. Epigenetic regulation in bovine cells: nutrient-induced modulation of gene expression and cellular functions. International Plant and Animal Genome IX Conference.

Interpretive Summary:

Technical Abstract: Research on nutrigenomics, the genome-nutrient interface and epigenomics is in its infancy with respect to livestock species. Ruminant species have evolved to metabolize short-chain fatty acids (VFA) to fulfill up to 70% of their energy requirements. Our studies revealed that VFA, especially butyrate, participate in metabolism as nutrients and as inhibitors of histone deacetylases (HDAC), which are one of the most important types of epigenetic regulators. 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. Butyrate Induced cell cycle arrest in bovine cells through targeting gene expression relevant to DNA replication apparatus. Our results also suggest that IGF2, not IGF1, along with its receptor (IGF2R) played a critical role in regulating cell cycle progression and programmed cell death. 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.