Chromatin profiling of the innate immune response in bovine MDBK cells

Cattle are an important livestock species, and understanding the genomic architecture of agriculturally relevant traits such as disease susceptibility is of major interest in the bovine research community. Lineage-specific transposable elements (TEs) are a source of interferon-gamma (IFNG)-inducible regulatory elements that control human immune genes, but this possibility has been largely unexplored in other species that harbor distinct transposon landscapes, including cattle. We conducted transcriptomic and epigenomic profiling of the IFNG response in bovine cells, and found that ruminant-specific TEs are a major source of IFNG-inducible enhancer elements that shape bovine innate immune responses. CRISPR knockout experiments established that key immune genes including bovine IFNAR2 and IL2RB are regulated by TEs in MDBKs. Together with previous work in human cells, our findings demonstrate that lineage-specific TEs have been independently co-opted to regulate IFNG-inducible gene expression in at least two mammalian lineages. Therefore, TE co-option may mediate parallel evolutionary rewiring of mammalian immune regulation. Overall design: Chromatin profiling (ATAC-seq) of a bovine cell line (MDBK) that was either untreated or treated with 100 ng/mL interferon gamma for 4h.