Submitted to: Genetics and Epigenetics
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/21/2014
Publication Date: 3/17/2014
Citation: Li, C., Li, R.W. 2014. Bioinformatic dissecting of TP53 regulation pathway underlying butyrate-induced histone modification in epigenetic regulation. Genetics and Epigenetics. Doi: 10.4137/GEG.S14176. Interpretive Summary: Butyrate is a major nutrient for cattle and is a regulator of cellular functions. The TP53 pathway regulates many cellular functions and may be a mediator of butyrate’s effects on cattle cells. Using modern bioinformatics software and data mining, we investigated the role of the TP53 pathway in butyrate-induced cellular functions of cattle. The results indicated that the TP53 pathways is activated in response to butyrate treatment. Nine transcription factors that are downstream regulators in TP53 signaling pathways were identified. These findings improve our basic understanding of how butyrate changes cellular functions in cattle cells and can be used by animal scientists to manipulate cellular functions through butyrate treatment.
Technical Abstract: Butyrate affects cell proliferation, differentiation and motility. Butyrate inhibits histone deacetylase (HDAC) activities and induces cell cycle arrest and apoptosis. TP53 is one of the most active upstream regulators discovered by IPA in our RNA sequencing data set. The TP53 signaling pathway plays a key role in many cellular processes. The TP53 pathway and its involvement in cellular functions modified by butyrate treatment were scrutinized in this report by data-mining the RNA sequencing data using Ingenuity Pathways Analysis (IPA, Ingenuity® System). The TP53 mechanistic pathway targets more than 600 genes. Downstream analysis predicated the activation of the TP53 pathway after butyrate treatment. The data mining also revealed that nine transcription factors are downstream regulators in TP53 signaling pathways. The analysis results also indicated that butyrate not only inhibits the HDAC activities, but also regulates genes encoding the HDAC enzymes through modification of histones and the epigenomic landscape. These findings will facilitate our understanding of the molecular mechanisms underlying butyrate-induced epigenomic regulation in bovine cells.