Studies performed using Hi-C and other high-throughput whole-genome C-methods have demonstrated that 3D organization of eukaryotic genomes is functionally relevant. Unfortunately, ultra-deep sequencing of Hi-C libraries necessary to detect loop structures in large vertebrate genomes remains rather expensive. However, many studies are in fact aimed at determining the fine-scale 3D structure of comparatively small genomic regions up to several Mb in length. Such studies typically focus on the spatial structure of domains of coregulated genes, molecular mechanisms of loop formation, and interrogation of functional significance of GWAS-revealed polymorphisms. Therefore, a handful of molecular techniques based on Hi-C have been developed to address such issues. These techniques commonly rely on in-solution hybridization of Hi-C/3C-seq libraries with pools of biotinylated baits covering the region of interest, followed by deep sequencing of the enriched library. Here, we describe a new protocol of this kind, C-TALE (Chromatin TArget Ligation Enrichment). Preparation of hybridization probes from bacterial artificial chromosomes and an additional round of enrichment make C-TALE a cost-effective alternative to existing many-versus-all C-methods.

中文翻译：

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C-TALE，一种新的具有成本效益的 Hi-C/3C-seq 文库靶向富集方法

使用 Hi-C 和其他高通量全基因组 C 方法进行的研究表明，真核基因组的 3D 组织在功能上是相关的。不幸的是，检测大型脊椎动物基因组中环结构所需的 Hi-C 文库的超深度测序仍然相当昂贵。然而，许多研究实际上旨在确定长达数 Mb 的相对较小的基因组区域的精细 3D 结构。这些研究通常集中在共调节基因域的空间结构、环形成的分子机制以及对 GWAS 揭示的多态性的功能意义的询问上。因此，已经开发了一些基于 Hi-C 的分子技术来解决这些问题。这些技术通常依赖于 Hi-C/3C-seq 文库与覆盖感兴趣区域的生物素化诱饵池的溶液内杂交，然后对富集文库进行深度测序。在这里，我们描述了一种新的协议，C-TALE（染色质目标连接富集）。从细菌人工染色体制备杂交探针和额外的一轮富集使 C-TALE 成为现有多对全 C 方法的经济高效的替代方案。