Profiling the immune epigenome across global cattle breeds.

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 analyse 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. 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. 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. The online version contains supplementary material available at 10.1186/s13059-023-02964-3.

了解适应良好和适应不良的牛品种在当地环境和病原体方面的差异，对于培育具有更好的气候适应性和抗病表型的牛至关重要。尽管在识别品种间的遗传差异方面已经取得了相当大的进展，但表观遗传和染色质水平的变异仍然特征不明显。在此，我们以碱基对分辨率生成、测序和分析了150多个文库，以探索三个不同牛谱系的牛免疫系统的DNA甲基化和染色质可及性的动态变化。 我们发现，在不同免疫细胞类型中，黄牛和瘤牛品种之间存在广泛的表观遗传差异，这与这两个牛亚种之间的局部DNA序列差异水平有关。独特的细胞类型图谱使得利用数字细胞计数方法对复杂的细胞混合物进行解卷积成为可能。最后，我们根据染色质和甲基化图谱展示了不同的CpG岛亚类，这些亚类可区分与离散转录状态相关的远端和基因近端岛屿类别。 我们的研究提供了三个不同牛种群的DNA甲基化、染色质可及性和RNA表达图谱的综合资源。这些发现具有重要意义，从理解不同品种间的基因编辑以及相应的调控背景可能产生的不同影响，到设计针对非欧洲品种的有效的牛全表观基因组关联研究。 网络版包含补充材料，可在10.1186/s13059 - 2023 - 02964 - 3获取。