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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 Elsasser, Theodore
item Li, Robert

Submitted to: Animal Genetics
Publication Type: Book / Chapter
Publication Acceptance Date: 3/24/2009
Publication Date: 11/24/2009
Citation: Li, C., Elsasser, T.H., Li, R.W. 2009. Epigenetic regulation in bovine cells: Nutrient-induced modulation of gene expression and cellular functions. In: Rech, Leopold J., editor. Animal Genetics. Nova Science Pubilshers, Inc. (ISBN:978-60741-844-3).

Interpretive Summary: Nutrigenetics is to study the interactions between the genome and nutrients and it is part of epigenetics. It is still in its infancy with respect to livestock species. Ruminant species use 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 (cell death) 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, 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.

Technical Abstract: Research on epigenetics and nutrigenetics, the genome-nutrient interface 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 provide a 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.