Integrated mapping of the dog epigenome (MBD-seq). Integrated mapping of the dog epigenome (MBD-seq)

Dogs have become a valuable model in exploring multifaceted diseases and biology relevant to human health. Despite large-scale dog genome projects producing high-quality draft references, a comprehensive annotation of functional elements is still lacking. We addressed this through integrative next-generation sequencing of transcriptomes paired with five histone marks and DNA methylome profiling across 11 tissue types, deciphering the dog’s epigenetic code by defining distinct chromatin states, super-enhancer and methylome landscapes, and thus showed that these regions are associated with a wide range of biological functions and cell/tissue identity. In addition, we confirmed that the phenotype-associated variants are enriched in tissue-specific regulatory regions and, therefore, the tissue of origin of the variants can be traced. Ultimately, we delineated conserved and dynamic epigenomic changes at the tissue- and species-specific resolutions. Our study provides an epigenomic blueprint of the dog that can be used for comparative biology and medical research. Overall design: 33 MBD-seq (22 MBD and 11 input data) generated from 11 adult normal tissue types of 3 beagles

犬类已成为探究与人类健康相关的多维度疾病及生物学过程的珍贵模型。尽管大规模犬类基因组计划已产出高质量参考基因组草图，但目前仍缺乏针对功能元件的全面注释。针对这一问题，本研究对11种组织类型的转录组开展整合型下一代测序（next-generation sequencing，NGS），同时结合五种组蛋白修饰标记与DNA甲基化组谱分析，通过界定不同染色质状态、超级增强子（super-enhancer）与甲基化组图谱，解析了犬类的表观遗传密码，进而证实这些区域广泛参与多种生物学功能及细胞/组织身份的维持。此外，本研究证实表型相关变异在组织特异性调控区域中显著富集，由此可追溯此类变异的起源组织。最终，本研究在组织与物种特异性分辨率层面，阐明了保守且动态的表观基因组变化规律。本研究构建了犬类的表观基因组蓝图，可用于比较生物学与医学研究。实验整体设计：从3只比格犬的11种成年正常组织中获取样本，共生成33份甲基结合蛋白测序（MBD-seq）数据（其中22份为MBD测序数据，11份为输入对照数据）