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Updated: Jul 27, 2025

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Hi-C: A Method to Study the Three-dimensional Architecture of Genomes.
Published on: May 6, 2010
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Linking genome structures to functions by simultaneous single-cell Hi-C and RNA-seq.
Zhiyuan Liu1,2, Yujie Chen1,2, Qimin Xia1,2
1Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China.
Summary
A new method, Hi-C and RNA-seq employed simultaneously (HiRES), links 3D genome structure to gene expression in single cells. This reveals how chromatin rewiring precedes gene activation during cell development.
Area of Science:
- Genomics and Molecular Biology
- Developmental Biology
- Epigenetics
Background:
- Single-cell chromosome conformation capture technologies have advanced significantly.
- A method for simultaneous profiling of chromatin architecture and gene expression was lacking.
Purpose of the Study:
- To develop and apply a novel assay for simultaneous single-cell chromatin architecture and gene expression profiling.
- To investigate the dynamics of 3D genome structure during mouse embryonic development.
Main Methods:
- Development of the Hi-C and RNA-seq employed simultaneously (HiRES) assay.
- Application of HiRES to thousands of single cells from developing mouse embryos.
Main Results:
- Single-cell 3D genome structures showed cell type-specific divergence during development, influenced by cell cycle and developmental stage.
- Pseudotemporal analysis revealed widespread chromatin rewiring preceding transcriptional activation.
- Established chromatin interactions are closely linked to transcriptional control and cell functions in lineage specification.
Conclusions:
- The HiRES assay enables simultaneous analysis of genome architecture and gene expression at the single-cell level.
- Chromatin rewiring plays a critical role in regulating gene expression and cell fate during development.
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