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Single-cell Micro-C profiles 3D genome structures at high resolution and characterizes multi-enhancer hubs

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Bibliographic Details
Title: Single-cell Micro-C profiles 3D genome structures at high resolution and characterizes multi-enhancer hubs
Authors: Honggui Wu, Jiankun Zhang, Longzhi Tan, Xiaoliang Sunney Xie
Source: Nat Genet
Publisher Information: Springer Science and Business Media LLC, 2025.
Publication Year: 2025
Subject Terms: Technical Report
Description: In animal genomes, regulatory DNA elements called enhancers govern precise spatiotemporal gene expression patterns in specific cell types. However, the spatial organization of enhancers within the nucleus to regulate target genes remains poorly understood. Here we report single-cell Micro-C (scMicro-C), a micrococcal nuclease-based three-dimensional (3D) genome mapping technique with an improved spatial resolution of 5 kb, and identified a specialized 3D enhancer structure termed ‘promoter–enhancer stripes (PESs)’, connecting a gene’s promoter to multiple enhancers. PES are formed by cohesin-mediated loop extrusion, which potentially brings multiple enhancers to the promoter. Further, we observed the prevalence of multi-enhancer hubs on genes with PES within single-cell 3D genome structures, wherein multiple enhancers form a spatial cluster in association with the gene promoter. Through its improved resolution, scMicro-C elucidates how enhancers are spatially coordinated to control genes.
Document Type: Article
Other literature type
Language: English
ISSN: 1546-1718
1061-4036
DOI: 10.1038/s41588-025-02247-6
Rights: CC BY
Accession Number: edsair.doi.dedup.....992f169ef26d8766e0d17ac918b97e63
Database: OpenAIRE
Description
Abstract:In animal genomes, regulatory DNA elements called enhancers govern precise spatiotemporal gene expression patterns in specific cell types. However, the spatial organization of enhancers within the nucleus to regulate target genes remains poorly understood. Here we report single-cell Micro-C (scMicro-C), a micrococcal nuclease-based three-dimensional (3D) genome mapping technique with an improved spatial resolution of 5 kb, and identified a specialized 3D enhancer structure termed ‘promoter–enhancer stripes (PESs)’, connecting a gene’s promoter to multiple enhancers. PES are formed by cohesin-mediated loop extrusion, which potentially brings multiple enhancers to the promoter. Further, we observed the prevalence of multi-enhancer hubs on genes with PES within single-cell 3D genome structures, wherein multiple enhancers form a spatial cluster in association with the gene promoter. Through its improved resolution, scMicro-C elucidates how enhancers are spatially coordinated to control genes.
ISSN:15461718
10614036
DOI:10.1038/s41588-025-02247-6