Chromatin physical interactions provide essential information for understanding the regulation of cis-elements like enhancers, promoters, and insulators in cell development and differentiation. The Hi-C assay is a technique detecting chromatin structures of the whole genome, but not sensitive to interactions of regulatory elements. Several methods, like HiChIP, DNase-C, and OCEAN-C, have been developed for enriching interactions of regulatory regions, but all of them have some shortcomings. New simple, efficient, and robust methods are still in need for detecting interactions of regulatory regions. We developed a new, simple, and robust assay called CoP (Column Purified chromatin) for profiling of open chromatin regions by directly purifying fragmentized crosslinked chromatin with a DNA purification column. The accessible chromatin regions, including active enhancers, promoters, and insulators, were significantly enriched in CoP chromatin. The CoP-seq assay can efficiently detect open chromatin regions, especially active promoters, with a high signal-to-noise ratio. We integrated the CoP-seq and Hi-C technique (HiCoP) to detect interactions of accessible chromatin regions, which represent active cis-regulatory elements in cells. We observed that the HiCoP captured the peaks in the promoters-associated enhancer regions. HiCoP detected more promoter–enhancer (P–E), promoter–promoter (P–P), and enhancer–enhancer (E–E) interactions within 20 kb–5 Mb than Hi-C. Most of the loops identified by HiCoP are associated with the expressed genes. CoP assay can efficiently enrich open chromatin regions. When CoP assay was integrated with Hi-C assay, it provides a simple, robust, alternative technique for profiling accessible chromatin regions and chromatin conformation simultaneously.

中文翻译：

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HiCoP，一种用于检测调控区域相互作用的简单而可靠的方法。

染色质的物理相互作用为理解细胞发育和分化过程中诸如增强子，启动子和绝缘子等顺式元素的调控提供了重要信息。Hi-C分析是一种检测整个基因组染色质结构的技术，但对调节元件的相互作用不敏感。已经开发了多种方法，如HiChIP，DNase-C和OCEAN-C，以丰富调控区域的相互作用，但它们都有一些缺点。仍需要新的简单，有效和强大的方法来检测调节区域的相互作用。我们开发了一种新的，简单而强大的测定方法，称为CoP（柱纯化的染色质），用于通过使用DNA纯化柱直接纯化片段化的交联染色质来分析开放的染色质区域。可访问的染色质区域 包括活性增强剂，启动子和绝缘子在内的CoP染色质明显丰富。CoP-seq分析可有效检测具有高信噪比的开放染色质区域，尤其是活性启动子。我们集成了CoP-seq和Hi-C技术（HiCoP），以检测可访问的染色质区域的相互作用，该区域代表细胞中活跃的顺式调控元件。我们观察到，HiCoP捕获了与启动子相关的增强子区域中的峰。与Hi-C相比，HiCoP在20 kb-5 Mb范围内检测到更多的启动子-增强子（P-E），启动子-启动子（P-P）和增强子-增强子（E-E）相互作用。HiCoP鉴定的大多数环与表达的基因相关。CoP分析可有效富集开放的染色质区域。将CoP分析与Hi-C分析整合后，它提供了一种简单，强大，