Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers

Author:

Xie Yeming,Ruan Fengying,Li Yaning,Luo Meng,Zhang Chen,Chen Zhichao,Xie Zhe,Weng Zhe,Chen Weitian,Chen Wenfang,Fang Yitong,Sun Yuxin,Guo Mei,Wang Juan,Xu Shouping,Wang Hongqi,Tang Chong

Abstract

AbstractAs the genome is organized into a three-dimensional structure in intracellular space, epigenomic information also has a complex spatial arrangement. However, most epigenetic studies describe locations of methylation marks, chromatin accessibility regions, and histone modifications in the horizontal dimension. Proper spatial epigenomic information has rarely been obtained. In this study, we designed spatial chromatin accessibility sequencing (SCA-seq) to resolve the genome conformation by simultaneously capturing the epigenetic information in single-molecular resolution. Using SCA-seq, we simultaneously disclosed spatial interaction of chromatin accessibility (e.g. enhancer-promoter contacts), CpG island methylation, and spatial insulating functions of the CCCTC-binding factor. We demonstrate that SCA-seq paves the way to explore the mechanism of epigenetic interactions and extends our knowledge in 3D packaging of DNA in the nucleus.

Publisher

Cold Spring Harbor Laboratory

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