Liu Xiaokun, Wei Hanhan, Zhang Qifan, Zhang Na, Wu Qingqing, Xu Chenhuan
China National Center for Bioinformation, Beijing, China.
Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Nat Commun. 2024 Dec 30;15(1):10922. doi: 10.1038/s41467-024-55403-7.
The proximity ligation-based Hi-C and derivative methods are the mainstream tools to study genome-wide chromatin interactions. These methods often fragment the genome using enzymes functionally irrelevant to the interactions per se, restraining the efficiency in identifying structural features and the underlying regulatory elements. Here we present Footprint-C, which yields high-resolution chromatin contact maps built upon intact and genuine footprints protected by transcription factor (TF) binding. When analyzed at one-dimensional level, the billions of chromatin contacts from Footprint-C enable genome-wide analysis at single footprint resolution, and reveal preferential modes of local TF co-occupancy. At pairwise contact level, Footprint-C exhibits higher efficiency in identifying chromatin structural features when compared with other Hi-C methods, segregates chromatin interactions emanating from adjacent TF footprints, and uncovers multiway interactions involving different TFs. Altogether, Footprint-C results suggest that rich regulatory modes of TF may underlie both local residence and distal chromatin interactions, in terms of TF identity, valency, and conformational configuration.
基于邻近连接的Hi-C及其衍生方法是研究全基因组染色质相互作用的主流工具。这些方法通常使用与相互作用本身功能无关的酶来切割基因组，限制了识别结构特征和潜在调控元件的效率。在此，我们介绍Footprint-C，它基于受转录因子（TF）结合保护的完整且真实的足迹生成高分辨率染色质接触图谱。在一维水平分析时，Footprint-C产生的数十亿个染色质接触能够以单足迹分辨率进行全基因组分析，并揭示局部TF共占据的优先模式。在成对接触水平上，与其他Hi-C方法相比，Footprint-C在识别染色质结构特征方面表现出更高的效率，分离出相邻TF足迹产生的染色质相互作用，并揭示涉及不同TF的多路相互作用。总之，Footprint-C的结果表明，就TF的身份、价态和构象配置而言，丰富的TF调控模式可能是局部驻留和远端染色质相互作用的基础。
