The dynamics of chromatin accessibility prompted by butyrate-induced chromatin modification in bovine cells

Authors: Boschiero, Clarissa; GAO, YAHUI - University Of Maryland; LIU, MEI - Hunan Agricultural University; Baldwin, Ransom - Randy; MA, LI - University Of Maryland; Li, Congjun - Cj; Liu, Ge - George

Submitted to: Ruminants
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/21/2022
Publication Date: 5/25/2022
Citation: Boschiero, C., Gao, Y., Liu, M., Baldwin, R.L., Ma, L., Li, C., Liu, G. 2022. The dynamics of chromatin accessibility prompted by butyrate-induced chromatin modification in bovine cells. Ruminants. 2(2):226-243. https://doi.org/10.3390/ruminants2020015.
DOI: https://doi.org/10.3390/ruminants2020015

Interpretive Summary: Butyrate plays important roles in rumen development. We studied open chromatin regions and regulatory elements in bovine cells treated with butyrate. These results fill our knowledge gaps and provide the foundation for incorporating new knowledge into the future animal breeding program. Farmers, scientist, and policy planners who need improve animal health and production based on genome-enabled animal selection will benefit from this study.

Technical Abstract: Background: Butyrate is a short-chain fatty acid produced by microbe fermentation that affects rumen development. Several cellular processes are modulated by butyrate in cells. Butyrate-induced biological responses are valuable in studying nutrient metabolism, cell growth, and functional regulation of genomic activities. This study aimed to identify and characterize accessible chromatin regions and the dynamics of genomic accessibility prompted by butyrate-induced histone modifications in bovine cells. Results: An average of 117,569 accessible chromatin regions (peaks) were identified for all butyrate samples. A total of 168,742 merged peaks for all samples, including shared and condition-specific regions, covering 2.78% of the cattle genome. From these accessible regions, 21,347 differentially accessible regions (DARs) were discovered in the butyrate. While 1,529 DARs were identified in promoter regions, most were located on distal intergenic regions and introns, including many enhancers regions, which were previously defined by epigenomic markers. Gene ontology enrichment results have shown several important GO terms related to the digestive system, the regulation of epithelial cells, tube development, anatomical structure formation involved in morphogenesis, regulation of cell adhesion, and cellular component movement. Ingenuity Pathway Analysis (IPA) identified critical networks (e.g., digestive system development and function, cell morphology and assembly, cellular function and maintenance, and cell cycle); canonical pathways (e.g., TGFBeta, Integrin-linked kinase, and epithelial adherens junction signaling), and upstream regulators (e.g., TGFBeta1, FOS, JUNB, ATF3, KLFs, MAPK1, and SMARCA4). Motif enrichment analyses of differentially accessible regions also revealed similar transcription factors, including ATF3, FOS, JUN, KLFs, and SMARCA4. Co-expression analysis further showcased the TGFß and Integrin-linked kinase (ILK) signaling pathways, which play roles in rumen development through cellular adhesions. Conclusions: This study is the first to provide a genome-wide characterization of differential open chromatin regions and regulatory elements for bovine cells by butyrate-induced treatment. These results provided valuable information for future studies of the butyrate functions in cattle gastrointestinal tract development and for the study of functional genomics in cattle.