Abstract
Short-chain fatty acids (SCFAs), especially butyrate, affect cell differentiation, proliferation, and motility. Butyrate also induces cell cycle arrest and apoptosis through its inhibition of histone deacetylases (HDACs). In addition, butyrate is a potent inducer of histone hyper-acetylation in cells. Therefore, this SCFA provides an excellent in vitro model for studying the epigenomic regulation of gene expression induced by histone acetylation. In this study, we analyzed the differential in vitro expression of genes induced by butyrate in bovine epithelial cells by using deep RNA-sequencing technology (RNA-seq). The number of sequences read, ranging from 57,303,693 to 78,933,744, were generated per sample. Approximately 11,408 genes were significantly impacted by butyrate, with a false discovery rate (FDR) <0.05. The predominant cellular processes affected by butyrate included cell morphological changes, cell cycle arrest, and apoptosis. Our results provided insight into the transcriptome alterations induced by butyrate, which will undoubtedly facilitate our understanding of the molecular mechanisms underlying butyrate-induced epigenomic regulation in bovine cells.
Highlights
Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are important nutrients in ruminants
Butyrate treatment induces changes in cell morphology and cell cycle arrest We previously reported that butyrate induces cell cycle arrest in MadinDarby bovine kidney epithelial cell line (MDBK) cells
In preparation for deep RNA sequencing, we first endeavored to confirm that the butyrate induced cell cycle arrest
Summary
Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are important nutrients in ruminants. SCFAs are produced during the microbial fermentation of dietary fiber in the gastrointestinal tract and are directly absorbed at the site of production and oxidized for cell energy production and use [1]. The SCFA butyrate, in particular, serves as an inhibitor of histone deacetylases (HDACs), which are critical epigenetic regulators [3,4,5]. Butyrate could act to reactivate epigenetically silenced genes by increasing global histone acetylation [6]. Epigenetic modifications play a key role in the regulation of gene expression, and HDAC activity contributes significantly to epigenetic modification. HDACs play significant roles in several human cancers, making HDAC inhibitors an important emerging class of chemotherapeutic agents
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