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

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 never 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 disclosed spatial regulation of chromatin accessibility (e.g. enhancer-promoter contacts) 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 genome architecture.

Long-read sequencing identifies copy-specific markers ofSMNgene conversion in spinal muscular atrophy

“…However, data on chromatin accessibility (H3K27ac ChIP-Seq and ATAC-seq), 3D DNA interactions (Hi-C) and DNA methylation are currently limited within the SMN locus, as this type of data is largely based on short-read sequencing and thus, does not map well on the SMN locus [28][29][30] or has not yet been studied in significant detail 31 . However, long-read methods for chromatin accessibility and interactions are emerging, and could prove useful in identifying regulatory regions within the SMN locus [32][33][34] . Similarly, methods to obtain information on base modifications such as methylation from long-read sequencing reads are increasingly sensitive and reliable 35,36 , opening possibilities to obtain this information concurrently with sequence and structural variation.…”

High efficient chromatin conformation capture without pre-enrichment (HiChew) in single cells

“…To further explore the relationship between gene expression and chromatin conformation, we're leveraging SCA-seq 12 , our multiomics chromatin conformation capture technology. This allows us to examine changes in chromatin accessibility and genome structure at a single molecule resolution.…”