To explore the bovine functional genomic elements and the vital roles of butyrate on the epigenetic modifications of bovine genomic activities, we generated and deposited the genome-wide datasets of transcript factor binding sites of CTCF (CCCTC-binding factor, insulator binding protein), histone methylation (H3H27me3, H3K4me1, H3K4me3) and histone acetylation (H3K27ac) from bovine rumen epithelial primary cells (REPC) before and after butyrate treatment (https://doi.org/10.1186/s12915-019-0687-8). This dataset provides detailed information on experiment design, data generation, data quality assessment and guideline for data re-use.