Osaka University, Suita, Osaka, Japan.
Biohistory Research Hall, Takatsuki, Osaka, Japan.
Results Probl Cell Differ. 2024;72:145-166. doi: 10.1007/978-3-031-39027-2_9.
Enhancers are the primary regulatory DNA sequences in eukaryotes and are mostly located in the non-coding sequences of genes, namely, intergenic regions and introns. The essential characteristic of an enhancer is the ability to activate proximal genes, e.g., a reporter gene in a reporter assay, regardless of orientation, relative position, and distance from the gene. These characteristics are ascribed to the interaction (spatial proximity) of the enhancer sequence and the gene promoter via DNA looping, discussed in the latter part of this chapter.Developmentally regulated genes are associated with multiple enhancers carrying distinct cell and developmental stage specificities, which form arrays on the genome. We discuss the array of enhancers regulating the Sox2 gene as a paradigm. Sox2 enhancers are the best studied enhancers of a single gene in developmental regulation. In addition, the Sox2 gene is located in a genomic region with a very sparse gene distribution (no other protein-coding genes in ~1.6 Mb in the mouse genome), termed a "gene desert," which means that most identified enhancers in the region are associated with Sox2 regulation. Furthermore, the importance of the Sox2 gene in stem cell regulation and neural development justifies focusing on Sox2-associated enhancers.
增强子是真核生物中主要的调控 DNA 序列，大多位于基因的非编码序列中，即基因间区和内含子。增强子的重要特征是能够激活近端基因，例如报告基因在报告基因检测中，无论方向、相对位置和与基因的距离如何。这些特征归因于增强子序列和基因启动子通过 DNA 环化的相互作用（空间接近），这将在本章的后半部分讨论。发育调节基因与携带不同细胞和发育阶段特异性的多个增强子相关，这些增强子在基因组上形成阵列。我们将 Sox2 基因的增强子阵列作为一个范例进行讨论。Sox2 增强子是发育调控中单基因的研究最深入的增强子之一。此外，Sox2 基因位于基因组区域，该区域基因分布非常稀疏（在小鼠基因组中约 1.6 Mb 范围内没有其他编码蛋白质的基因），称为“基因荒漠”，这意味着该区域大多数已识别的增强子都与 Sox2 调节有关。此外，Sox2 基因在干细胞调节和神经发育中的重要性证明了关注 Sox2 相关增强子是合理的。
