Chromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogeneous and simple systems, such as isolated cell populations or early-development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, we use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism Caenorhabditis elegans, from embryogenesis to adulthood. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development. We find that over 5000 distal noncoding regions exhibit dynamic changes in chromatin accessibility between developmental stages and could thereby represent putative enhancers. When tested in vivo, several of these putative enhancers indeed drive novel cell-type- and temporal-specific patterns of expression. Finally, by integrating transcription factor binding motifs in a machine learning framework, we identify EOR-1 as a unique transcription factor that may regulate chromatin dynamics during development. Our study provides a unique resource for C. elegans, a system in which the prevalence and importance of enhancers remains poorly characterized, and demonstrates the power of using whole organism chromatin accessibility to identify novel regulatory regions in complex systems.

染色质可及性是基因组调控的重要组成部分，主要在均质且简单的系统中进行了研究，例如分离的细胞群或早期发育模型。能否在体内复杂，动态的系统中以高灵敏度评估染色质的可及性，仍需大量研究。在这项研究中，我们使用ATAC-seq识别整个动物（模型生物秀丽隐杆线虫）中的染色质可及性变化，从胚胎发育到成年。发育阶段之间的染色质可及性变化是高度可重现的，概括了组蛋白修饰变化，并揭示了整个生物发育过程中表观基因组景观的关键调控方面。我们发现，超过5000个远端非编码区在各个发育阶段之间表现出染色质可及性的动态变化，从而可以代表推定的增强子。当在体内进行测试时，这些推定的增强子中的几种确实驱动了新型的细胞类型和时间特异性表达模式。最后，通过在机器学习框架中整合转录因子结合基序，我们将EOR-1确定为可能在发育过程中调节染色质动力学的独特转录因子。我们的研究为秀丽隐杆线虫提供了独特的资源，该系统中增强剂的普遍性和重要性仍然很差，并且证明了使用整个生物体染色质可及性来鉴定复杂系统中新的调控区的能力。