Profiling the immune epigenome across global cattle breeds

Jess Powell*, Andrea Talenti*, Andressa Fisch, Hanneke Hemmink, Edith Paxton, Philip Toye, Isabel Santos, Beatriz Rossetti Ferreira, Tim Connelley, Liam Morrison, James Prendergast*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background
Understanding the variation between well and poorly adapted cattle breeds to local environments and pathogens is essential for breeding cattle with improved climate and disease resistant phenotypes. Although considerable progress has been made towards identifying genetic differences between breeds, variation at the epigenetic and chromatin levels remains poorly characterized. Here, we generate, sequence and analyze over 150 libraries at base-pair resolution to explore the dynamics of DNA methylation and chromatin accessibility of the bovine immune system across three distinct cattle lineages.
Results
We find extensive epigenetic divergence between the taurine and indicine cattle breeds across immune cell types, which is linked to the levels of local DNA sequence divergence between the two cattle sub-species. The unique cell type profiles enable the deconvolution of complex cellular mixtures using digital cytometry approaches. Finally, we show distinct sub-categories of CpG islands based on their chromatin and methylation profiles that discriminate between classes of distal and gene proximal islands linked to discrete transcriptional states.
Conclusions
Our study provides a comprehensive resource of DNA methylation, chromatin accessibility and RNA expression profiles of three diverse cattle populations. The findings have important implications, from understanding how genetic editing across breeds, and consequently regulatory backgrounds, may have distinct impacts, to designing effective cattle epigenome-wide association studies in non-European breeds.
Original languageEnglish
Article number127
Pages (from-to)1-31
Number of pages31
JournalGenome Biology
Volume24
Early online date22 May 2023
DOIs
Publication statusPublished - 22 May 2023

Keywords / Materials (for Non-textual outputs)

  • Cattle
  • subspecies
  • DNA methylation
  • chromatin
  • expression
  • immune cells

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