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Updated: Jul 15, 2026
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Mapping Mammalian 3D Genome Interactions with Micro-C-XL
Published on: November 3, 2023
Mapping 3D genome organization at nucleosome-scale with Micro-C and Region Capture Micro-C (RCMC)
Miles K Huseyin1,2,3,4, Clarice K Y Hong1,2,3,4, Masahiro Nagano1,2,3,4
1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature Protocols
|July 13, 2026
Summary
Micro-C and Region Capture Micro-C (RCMC) offer nucleosome-scale resolution of 3D genome organization. These chromosome conformation capture methods improve upon Hi-C by identifying fine-scale genomic interactions.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Chromosome conformation capture (3C) methods reveal genome 3D organization.
- Previous methods like Hi-C have limitations in resolution and reliance on restriction enzymes.
Purpose of the Study:
- To introduce Micro-C and Region Capture Micro-C (RCMC) as advanced 3C techniques.
- To achieve nucleosome-scale resolution of 3D genome organization and identify novel genomic interactions.
Main Methods:
- Micro-C involves in situ MNase digestion, crosslinking, ligation, and biotin pulldown of nucleosomal DNA.
- RCMC adds a capture step for targeted enrichment of specific genomic regions.
- These methods avoid sequence motifs and size-select for mononucleosomes, unlike restriction enzyme-based methods.
Main Results:
- Micro-C achieves nucleosome-scale resolution of 3D genome organization.
- It identifies known 3D genome features and interactions, including enhancer-promoter links missed by prior techniques.
- RCMC provides enhanced depth and finer resolution of interactions.
Conclusions:
- Micro-C and RCMC significantly advance the study of 3D genome architecture.
- These methods offer a faster, more precise alternative for investigating genome organization at the nucleosome level.
- RCMC enables cost-effective deep sequencing of specific genomic regions.
