Comparative functional genome annotation of livestock species identifies core amniote regulatory features and avian enhancer versatility (H3K4me3 ChIP-Seq)

Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. Here we present a genome-wide annotation of regulatory elements in a non-mammalian vertebrate, chicken (Gallus gallus), as well as two important agricultural mammalian species: pig (Sus scrofa) and cattle (Bos taurus), with chicken and pig in particular being important to human biology and medicine. This report is the first to employ all core assays as defined by the Functional Annotation of Animal Genomes (FAANG) consortium, including information from a wide range of epigenomic assays for the same eight diverse tissues of three livestock species. Comparative analysis of these datasets and those from the human and mouse ENCODE projects revealed that although less than half of enhancers are positionally conserved between species, a core set of regulatory elements are functionally conserved independent of evolutionary distance. Further analysis suggested that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes were also conserved. Interestingly, the smaller chicken genome – relative to mammals – contains a reduced number of enhancers; however, each chicken enhancer targets more genes, on average, compared to their mammalian counterparts suggesting higher versatility. These datasets and corresponding analysis represent a unique opportunity for the emerging field of comparative epigenomics, as well as animal and human biology and medical research involving species that are globally important food resources. H3K4me3 ChIP-seq in 8 tissues from 3 livestock species (2 adult male replicates per species)

基因调控元件是表型变异的核心驱动因素，因此对于解析复杂性状的遗传机制至关重要。本研究完成了非哺乳类脊椎动物鸡（Gallus gallus），以及两种重要农业哺乳类物种：猪（Sus scrofa）和牛（Bos taurus）的全基因组调控元件注释，其中鸡与猪对人类生物学与医学研究具有重要价值。本报告是首个采用动物基因组功能注释（Functional Annotation of Animal Genomes, FAANG）联盟定义的全部核心实验方法的研究，涵盖了三种家畜物种共8种不同组织的多组表观基因组检测数据。通过对本数据集与人类、小鼠ENCODE计划数据集的比较分析发现：尽管仅不足半数的增强子在物种间存在位置保守性，但存在一类核心调控元件，其功能保守性与进化距离无关。进一步分析表明，调控元件上的组织特异性转录因子结合位点及其预测靶基因同样具有保守性。值得注意的是，相较于哺乳类动物，鸡的基因组尺寸更小，所含增强子数量更少；但平均而言，每个鸡源增强子调控的靶基因数量多于哺乳类同源增强子，这提示鸡的调控元件具有更高的多功能性。本数据集及配套分析为新兴的比较表观基因组学领域，以及以全球重要食用经济物种为研究对象的动物、人类生物学与医学研究提供了独特的研究契机。本数据集包含三种家畜物种（每个物种2份成年雄性生物学重复）的8种组织的H3K4me3染色质免疫共沉淀测序（ChIP-seq）数据。