?High-resolution 3D genome structures via single-cell Micro-C uncovers cohesin-?mediated enhancer-promoter loops (SDS test)
In the metazoan genome, regulatory DNA elements called enhancers govern the precise spatiotemporal patterns of gene expression in specific cell types. However, how enhancers are spatially organized to regulate target genes remains poorly understood. Here, by improving the spatial resolution of single-cell 3D genome mapping to 5 kb with micrococcal nuclease in our new single-cell Micro-C method, we report a specialized 3D structure of enhancers termed “promoter stripes,” which start at the transcription start site (TSS) and extend in the direction of transcription on the contact map, linking the promoter to multiple downstream enhancers. Promoter stripes are formed by cohesin-mediated loop extrusion, which potentially brings multiple enhancers to the promoter. Furthermore, with high-resolution single-cell chromatin structures, we observed the prevalence of multi-enhancer hubs on genes with promoter stripes, wherein multiple enhancers form spatial cluster associating its promoter. Such observation was only made possible by single-cell 3D genome with the improved resolution. Overall design: Single-cell Micro-C (with and without the addition of SDS)