Successful development depends on the precise tissue‐specific regulation of genes by enhancers, genetic elements that act as switches to control when and where genes are expressed. Because enhancers are critical for development, and the majority of disease‐associated mutations reside within enhancers, it is essential to understand which sequences within enhancers are important for function. Advances in sequencing technology have enabled the rapid generation of genomic data that predict putative active enhancers, but functionally validating these sequences at scale remains a fundamental challenge. Herein, we discuss the power of genome‐wide strategies used to identify candidate enhancers, and also highlight limitations and misconceptions that have arisen from these data. We discuss the use of massively parallel reporter assays to test enhancers for function at scale. We also review recent advances in our ability to study gene regulation during development, including CRISPR‐based tools to manipulate genomes and single‐cell transcriptomics to finely map gene expression. Finally, we look ahead to a synthesis of complementary genomic approaches that will advance our understanding of enhancer function during development.

中文翻译：

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功能基因组方法阐明增强子在发育过程中的作用。

成功的发育取决于增强子对基因的精确组织特异性调节，增强子是充当控制基因表达时间和地点的开关的遗传元件。由于增强子对于发育至关重要，并且大多数与疾病相关的突变都存在于增强子内，因此有必要了解增强子内的哪些序列对功能很重要。测序技术的进步使得能够快速生成基因组数据来预测假定的活性增强子，但大规模地对这些序列进行功能验证仍然是一个基本挑战。在这里，我们讨论了用于识别候选增强子的全基因组策略的力量，并强调了这些数据产生的局限性和误解。我们讨论了使用大规模并行报告基因检测来大规模测试增强剂的功能。我们还回顾了研究发育过程中基因调控能力的最新进展，包括基于 CRISPR 的工具来操纵基因组和单细胞转录组学来精细绘制基因表达图谱。最后，我们期待互补基因组方法的综合，这将增进我们对发育过程中增强子功能的理解。