Rapid and Pervasive Changes in Genome-Wide Enhancer Usage During Mammalian Development. Mus musculus

Here we used epigenomic profiling for H3K27ac, a mark of active enhancers to examine the genome-wide in vivo utilization of enhancers in three different mouse tissues across seven developmental stages, ranging from mid-gestation through adulthood. The majority of the ~90,000 enhancers identified exhibited tightly temporally restricted activity windows and were associated with stage-specific biological functions and regulatory pathways in individual tissues. Comparative genomic analysis revealed that evolutionary conservation of enhancers decreases following mid-gestation across all tissues examined. The dynamic enhancer activities uncovered in this study illuminate rapid and pervasive temporal in vivo changes in enhancer usage underlying developmental processes and demonstrate the value of time-course chromatin profiling of relevant tissues across development. Overall design: Examination of H3K27ac in mouse forebrain, heart and liver tissues collected across developmental stages.

本研究采用针对活性增强子标记物组蛋白H3赖氨酸27乙酰化（H3K27ac）的表观基因组谱分析技术，对覆盖从中妊娠至成年七个发育阶段的三种小鼠组织，开展全基因组范围内的增强子体内利用情况检测。本研究共鉴定出约9万个增强子，其中绝大多数呈现严格的时间限制性活性窗口，并在各对应组织中与阶段特异性生物学功能及调控通路显著关联。比较基因组分析结果显示，在所检测的全部组织中，增强子的进化保守性在中妊娠阶段后呈下降趋势。本研究揭示的动态增强子活性，阐明了驱动发育进程的增强子使用模式所伴随的快速且广泛的体内时间动态变化，并证实了跨发育阶段对相关组织开展时序染色质谱分析的重要价值。整体实验设计：对不同发育阶段采集的小鼠前脑、心脏及肝脏组织中的H3K27ac进行检测。