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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Genomics and Improvement Laboratory » Research » Publications at this Location » Publication #421136
Research Project: Accelerating Genetic Improvement of Ruminants Through Enhanced Genome Assembly, Annotation, and Selection

Location: Animal Genomics and Improvement Laboratory

Title: Profiling genome-wide methylation patterns in cattle infected with Ostertagia ostertagi

Author
item BOSCHIERO, CLARISSA - Collaborator
item Beshah, Ethiopia
item ZHU, XIAOPING - University Of Maryland
item Tuo, Wenbin
item Liu, Ge

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/17/2024
Publication Date: 12/26/2024
Citation: Boschiero, C., Beshah, E., Zhu, X., Tuo, W., Liu, G.E. 2024. Profiling genome-wide methylation patterns in cattle infected with Ostertagia ostertagi. International Journal of Molecular Sciences. 26(1).Article e89. https://doi.org/10.3390/ijms26010089.
DOI: https://doi.org/10.3390/ijms26010089

Interpretive Summary: Parasite resistance is important for the animal industry. We analyzed DNA methylation changes in cattle tissues during nematode infection and provided insights into immune response and infection-related epigenetic regulation. These results fill our knowledge gaps and provide the foundation for incorporating new epigenetics insights into the future animal breeding program. Farmers, scientists, and policy makers who need to improve animal health and production based on genome-enabled animal selection will benefit from this study.

Technical Abstract: DNA methylation (DNAm) regulates gene expression and genomic imprinting, influencing traits like growth, reproduction, and disease resistance. While DNAm patterns in specific cattle tissues have been studied, the effects of gastrointestinal (GI) nematode infection on DNAm remain largely unknown. Helminth-free Holstein steers (n=5) were trickle-infected orally with O. ostertagi stage 3 larvae in tap water (1,000 larvae/day) for 4 weeks, 5 days per week. Control animals (n=5) received tap water only. All animals were euthanized 30 days after the first infection and tissues were collected and stored at -80C until used. We conducted epigenome-wide profiling using the mammalian methylation array (HorvathMammalMethylChip40) and explored the impact of GI nematode infection on the methylation patterns in four different cattle tissues including mucosal tissues from duodenum (DUO), pyloric abomasum (PYL), and fundic abomasum (FUN) and abomasal draining lymph nodes (dLN) in infected and uninfected animals. The analysis covered 31,107 cattle CpGs of 5082 genes derived from 37 samples (19 infected and 18 noninfected tissues) and revealed infection-related, tissue-specific, differential methylation patterns. A total of 389 shared and 2770 tissue-specific differentially methylated positions (DMPs, 5% delta-beta) were identified in dLN and FUN, particularly in genes associated with immune responses. The shared DMPs were found in 263 genes where those relating to immune-response pathways are abundant (BCL11A, IFNG, IL20RB, IKZF1, LRFN5, NTRK2, PSMD7, SATB1, SMAD7, TFEC, TLE1, TLE3, TP63, ZEB2). Furthermore, 282, 244, 52, and 24 differentially methylated regions (DMRs, 10% delta-beta) were observed in dLN, FUN, PYL, and DUO, respectively. There were more hypomethylated DMRs detected in dLN and FUN, while more hypermethylated DMRs were found in PYL and DUO. Among the genes carrying DMPs and DMRs, immune-related genes including BCL11A, EPHB2, EGR3, FKBP5, FOSB, IL17B, IL20RB, IRX5, NTRK3, OIT3, RAB2A, RARA, SATB1, SATB2, SMAD4, TLE1/4, TLX3, and ZEB2 were revealed. We further uncovered enriched pathways related to immune functions in infected animals, indicating a link between DNA methylation changes and GI nematode infection. These pathways included WNT/Beta-catenin signaling, Th1 and Th2 activation, RAR activation, NGF-stimulated transcription, IL-15 production, and IL-4, 7, 12, and 13 signaling pathways. The data may implicate a crucial role of DNAm in regulating the nature and/or strength of host immunity to the infection, which will facilitate further understanding of immune evasion, a survival strategy commonly used by parasitic nematodes. Integration with RNA sequencing (RNA-seq) data additionally revealed genes related to immune functions, some of which are transcription factors. These findings contribute to a deeper understanding of the epigenetic regulatory landscape in cattle during GI nematode infection, highlighting potential targets for further investigation.