Enhancers are essential drivers of cell states, yet the relationship between accessibility, regulatory activity, and in vivo lineage commitment during embryogenesis remains poorly understood. Here, we measure chromatin accessibility in isolated neural and mesodermal lineages across a time course of Drosophila embryogenesis. Promoters, including tissue-specific genes, are often constitutively open, even in contexts where the gene is not expressed. In contrast, the majority of distal elements have dynamic, tissue-specific accessibility. Enhancer priming appears rarely within a lineage, perhaps reflecting the speed of Drosophila embryogenesis. However, many tissue-specific enhancers are accessible in other lineages early on and become progressively closed as embryogenesis proceeds. We demonstrate the usefulness of this tissue- and time-resolved resource to definitively identify single-cell clusters, to uncover predictive motifs, and to identify many regulators of tissue development. For one such predicted neural regulator, l(3)neo38, we generate a loss-of-function mutant and uncover an essential role for neuromuscular junction and brain development.

增强子是细胞状态的基本驱动因素，但胚胎发生过程中可及性、调节活动和体内谱系承诺之间的关系仍然知之甚少。在这里，我们在果蝇胚胎发生的整个时间过程中测量分离的神经和中胚层谱系中的染色质可及性。启动子，包括组织特异性基因，通常是组成型开放的，即使在基因未表达的情况下也是如此。相比之下，大多数远端元件具有动态的、特定于组织的可访问性。增强子启动很少出现在一个谱系中，这可能反映了果蝇的速度胚胎发生。然而，许多组织特异性增强子在早期可以在其他谱系中使用，并且随着胚胎发生的进行而逐渐关闭。我们证明了这种组织和时间分辨资源在明确识别单细胞簇、揭示预测基序和识别组织发育的许多调节剂方面的有用性。对于这样一个预测的神经调节器l(3)neo38，我们生成了一个功能丧失突变体，并揭示了神经肌肉接头和大脑发育的重要作用。