Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures.

Changes in the epigenetic regulation of gene expression have a central role in evolution. Here, we extensively profiled a panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS). We annotated regulatory elements (RE) and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of RE in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers (gE) in the regulation of gene expression. We observe that most regulatory changes occur in weakly active gE. Remarkably, novel human-specific gE with weak activities are enriched in human-specific nucleotide changes. These elements appear in genes with signals of positive selection and human acceleration, tissue-specific expression, and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation. Comparative epigenomics has revealed principles underlying the evolution of gene expression regulation, and the integration of epigenomic data is important for a deeper understanding of this evolution. Here the authors report the evolutionary dynamics of the epigenomic regulatory landscape in primates and their impact in recent human evolution.

基因表达的表观遗传调控变化在进化中起着核心作用。在此，我们对一组人类、黑猩猩、大猩猩、红猩猩和猕猴的淋巴母细胞系（LCLs）进行了广泛的分析，使用针对五种组蛋白标记的染色质免疫沉淀测序（ChIP - seq）、转座酶可及染色质测序（ATAC - seq）和RNA测序（RNA - seq），并进一步辅以全基因组测序（WGS）和全基因组亚硫酸氢盐测序（WGBS）。我们对调控元件（RE）进行注释，并整合染色质接触图谱以确定基因调控结构，创建了迄今为止灵长类动物中最大的调控元件目录。我们报告称，灵长类动物中的表观遗传保守性及其与序列保守性的相关性取决于调控元件的活性状态。我们的基因调控结构揭示了不同类型元件的协同作用，并强调了启动子和基因内增强子（gE）在基因表达调控中的作用。我们观察到大多数调控变化发生在弱活性的gE中。值得注意的是，具有弱活性的新型人类特异性gE富含人类特异性的核苷酸变化。这些元件出现在具有正选择和人类加速信号、组织特异性表达以及特定功能富集的基因中，表明这些基因的调控进化可能对人类适应有所贡献。 比较表观基因组学揭示了基因表达调控进化的基本原理，而表观基因组数据的整合对于更深入地理解这种进化至关重要。在此，作者报告了灵长类动物表观基因组调控景观的进化动态及其在近期人类进化中的影响。