Spatial chromatin accessibility sequencing resolves next-generation genome architecture

Abstract As the genome has a three-dimensional structure in intracellular space, epigenomic information also has a complex spatial arrangement. However, the majority of epigenetic studies describe locations of methylation marks, chromatin accessibility regions, and histone modifications in the linear dimension. Proper spatial epigenomic information has rarely been obtained. In this study, we designed spatial chromatin accessibility sequencing (SCA-seq) to reveal the three-dimensional map of chromatin accessibility and simultaneously capture the genome conformation. Using SCA-seq, we simultaneously disclosed spatial regulation 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 epigenomic information in the three-dimensional space and extends our knowledge in next-generation genome architecture.