Epigenetics

Shared Heat Stress-Induced Epigenetic Signatures at Immune-Related Loci in Two Independent Dairy Cow Cohorts

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Abstract

Heat stress represents a challenge for dairy production, affecting animal health and productivity. To uncover epigenomic mechanisms underlying its effects, we analyzed DNA methylation changes in blood from lactating cows exposed to acute heat stress using Reduced Representation Bisulfite Sequencing (RRBS). Two independent experiments were conducted in Canada and France, each with paired blood samples collected before and after heat stress exposure. In the Canadian cohort, four cows underwent a 14-day heat stress challenge (THI 72-82), while four were maintained under thermoneutral conditions (THI 61-64). Thermoneutral cows were pair-fed to match the intake of the heat-stressed group, allowing differences to be attributed primarily to thermal conditions rather than feed intake. Differential methylation analysis was performed between samples collected before and after heat stress exposure, excluding differentially methylated cytosines (DMCs) identified between the corresponding thermoneutrality periods (pair-fed group of cows). By adopting this approach, we identified 2,259 heat stress-specific DMCs. In the French cohort, six cows were exposed to two 7-day heat waves (average THI 70-75), separated by a 14-day recovery period. Paired analysis (before the first vs. after the second heat wave) detected 3,310 DMCs. Many DMCs were in intergenic or intronic regions - known to harbor cis-regulatory elements - and near genes related to immune system regulation and stress response. Cross-cohort comparison revealed 42 common DMCs, including three that consistently lost methylation within LTBP3 and INPP4A genes, associated with B- and T-cell functions, respectively. Although the absolute number of shared DMCs was modest relative to cohort-specific signals, the detection of shared loci with consistent direction of methylation change and functional relevance supports the existence of biologically meaningful epigenetic signatures across the independent experiments. Complementary CTCF-CUT&RUN assays showed co-localization of these common DMCs with CTCF binding sites, suggesting that heat stress induces altered chromatin architecture at immune-related loci. Overall, our results indicate that heat stress can trigger coordinated changes in DNA methylation and chromatin organization at immune-related genes in dairy cows. Further investigations will allow to assess whether these epigenetic marks could serve as potential biomarkers for identifying resilient cows to heat stress.

Keywords: 2026

How to Cite:

Costa Monteiro Moreira, G., Rey-Cadilhac, L., Hurtaud, C., Boudon, A., Ruiz-González, A., Jouin, M., Joigner, M., Costes, V., Ali, F., Chaulot-Talmon, A., Kiefer, H., Jammes, H., Rico, D. & Boutinaud, M., (2026) “Shared Heat Stress-Induced Epigenetic Signatures at Immune-Related Loci in Two Independent Dairy Cow Cohorts”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2286345. doi: https://doi.org/10.31274/wcgalp.23942

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