Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells

Abstract

Butyrate is produced in the rumen from microbial fermentation and is related to several functions, including cell differentiation and proliferation. Butyrate supplementation in calves can accelerate rumen development. DNA-protein interactions, such as the CCCTC-binding factor (CTCF), play essential roles in chromatin organization and gene expression regulation. Although CTCF-binding sites have been identified recently in cattle, a deeper characterization, including differentially CTCF-binding sites (DCBS), is vital for a better understanding of butyrate’s role in the chromatin landscape. This study aimed to identify CTCF-binding regions and DCBS under a butyrate-induced condition using ChIP-seq in bovine cells; 61,915 CTCF peaks were identified in the butyrate and 51,347 in the control. From these regions, 2265 DCBS were obtained for the butyrate vs. control comparison, comprising ~90% of induced sites. Most of the butyrate DCBS were in distal intergenic regions, showing a potential role as insulators. Gene ontology enrichment showed crucial terms for the induced DCBS, mainly related to cellular proliferation, cell adhesion, and growth regulation. Interestingly, the ECM-receptor interaction pathway was observed for the induced DCBS. Motif enrichment analysis further identified transcription factors, including CTCF, BORIS, TGIF2, and ZIC3. When DCBS was integrated with RNA-seq data, putative genes were identified for the repressed DCBS, including GATA4. Our study revealed promising candidate genes in bovine cells by a butyrate-induced condition that might be related to the regulation of rumen development, such as integrins, keratins, and collagens. These results provide a better understanding of the function of butyrate in cattle rumen development and chromatin landscape regulation.

Effect of Nanomaterials on Gut Microbiota

“…Short-chain fatty acids facilitate contact between the intestinal microbiota and the host, as well as the regulation of cell growth and differentiation [9][10][11]. For example, butyrate, which is the most abundant in production, at physiological concentrations promotes cell differentiation and inhibits growth [12,13]. Butyrate functions as an agonist of histone deacetylase (HDCA) inhibitors and histone transferases, boosting histone acetylation and promoting post-translational histone modification [14,15].…”

Genome-Wide Acetylation Modification of H3K27ac in Bovine Rumen Cell Following Butyrate Exposure

“…For farm animals, butyrate is reported to modulate the gut microbial metabolites [9] and the intestinal barrier [10,11], alleviate inflammation [12,13], and improve animal growth performance and meat quality [14,15]. All these might be achieved by butyrate-derived metabolic rewiring and genetic and epigenetic reprogramming, because butyrate could regulate gene expression changes by mediating multiple signal pathways [16][17][18] and epigenetic modification [7,[19][20][21] at a bulk and single-cell level.…”

“…Regarding the HDACi effect mediated by butyrate, we profiled the genome-wide transcriptome change [17], CTCF-binding regions [19], and functional annotation of chromatin states under the butyrate treatment in our previous studies. However, it remains unknown how the H3K27ac mark changes under this treatment in rumen epithelial primary cells (REPC) and how H3K27ac histone acetylome changes contribute to the phenotype response in REPC under the butyrate treatment.…”

Sodium Butyrate Induces Mitophagy and Apoptosis of Bovine Skeletal Muscle Satellite Cells through the Mammalian Target of Rapamycin Signaling Pathway

“…NaB reduces Ang II-induced NLRP3 inflammasome-related protein expression and repairs autophagy dysfunction due to lysosomal damage in macrophages [7]. For cattle, NaB induces profound changes in gene expression in bovine kidney epithelial cells, which were associated with cell cycle control [8,9]. In addition, NaB regulates chromatin state changes in bovine rumen epithelial primary cells [10,11] and promotes milk fat synthesis in bovine mammary epithelial cells [12].…”