Ruminant-specific retrotransposons shape regulatory evolution of bovine immunity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA767619 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16130017_1.fastq.gz | Fastqsanger.gz | |||
| SRR16130017_2.fastq.gz | Fastqsanger.gz | |||
| SRR16130018_1.fastq.gz | Fastqsanger.gz | |||
| SRR16130018_2.fastq.gz | Fastqsanger.gz | |||
| SRR16130019_1.fastq.gz | Fastqsanger.gz |
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Project description:Cattle are an important livestock species, and mapping the genomic architecture of agriculturally relevant traits such as disease susceptibility is a major challenge in the bovine research community. Lineage-specific transposable elements (TEs) are increasingly recognized to contribute to gene regulatory evolution and variation, but this possibility has been largely unexplored in ruminant genomes. We conducted epigenomic profiling of the type II interferon (IFN) response in bovine cells and found thousands of ruminant-specific TEs including MER41_BT and Bov-A2 elements predicted to act as IFN-inducible enhancer elements. CRISPR knockout experiments in bovine cells established that critical immune factors including IFNAR2 and IL2RB are transcriptionally regulated by TE-derived enhancers. Finally, population genomic analysis of 38 individuals revealed that a subset of polymorphic TE insertions may function as enhancers in modern cattle. Our study reveals that lineage-specific TEs have shaped the evolution of ruminant IFN responses and potentially continue to contribute to immune gene regulatory differences across modern breeds and individuals. Together with previous work in human cells, our findings demonstrate that lineage-specific TEs have been independently co-opted to regulate IFN-inducible gene expression in multiple species, supporting TE co-option as a recurrent mechanism driving the evolution of IFN-inducible transcriptional networks.
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Project description: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.
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Project description: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.
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