Department of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, Canada.
Genome. 2021 Apr;64(4):426-448. doi: 10.1139/gen-2020-0104. Epub 2020 Sep 22.
Enhancers are -regulatory sequences located distally to target genes. These sequences consolidate developmental and environmental cues to coordinate gene expression in a tissue-specific manner. Enhancer function and tissue specificity depend on the expressed set of transcription factors, which recognize binding sites and recruit cofactors that regulate local chromatin organization and gene transcription. Unlike other genomic elements, enhancers are challenging to identify because they function independently of orientation, are often distant from their promoters, have poorly defined boundaries, and display no reading frame. In addition, there are no defined genetic or epigenetic features that are unambiguously associated with enhancer activity. Over recent years there have been developments in both empirical assays and computational methods for enhancer prediction. We review genome-wide tools, CRISPR advancements, and high-throughput screening approaches that have improved our ability to both observe and manipulate enhancers in vitro at the level of primary genetic sequences, chromatin states, and spatial interactions. We also highlight contemporary animal models and their importance to enhancer validation. Together, these experimental systems and techniques complement one another and broaden our understanding of enhancer function in development, evolution, and disease.
增强子是位于靶基因远端的调控序列。这些序列整合了发育和环境线索，以组织特异性的方式协调基因表达。增强子的功能和组织特异性取决于表达的转录因子集合，这些转录因子识别结合位点并募集辅助因子，以调节局部染色质结构和基因转录。与其他基因组元件不同，增强子难以识别，因为它们的功能独立于定向，通常远离其启动子，边界定义不明确，并且不显示可读框。此外，没有明确的遗传或表观遗传特征与增强子活性明确相关。近年来，在增强子预测的经验性测定和计算方法方面都有了发展。我们综述了全基因组工具、CRISPR 技术的进步以及高通量筛选方法，这些方法提高了我们在体外观察和操作初级遗传序列、染色质状态和空间相互作用水平上增强子的能力。我们还强调了当代动物模型及其对增强子验证的重要性。这些实验系统和技术相互补充，拓宽了我们对增强子在发育、进化和疾病中的功能的理解。
