Single-cell Hi-C reveals cell-to-cell variability in chromosome structure

Area of Science:

• Genomics
• Molecular Biology
• Cell Biology

Background:

• Large-scale chromosome structure and nuclear organization influence gene expression, DNA replication, and repair.
• Chromosome conformation capture (3C) techniques provide population-averaged contact data, masking single-cell variability.

Purpose of the Study:

• To investigate single-cell chromosome structure and its relationship with genome activity.
• To bridge the gap between genomic and microscopy approaches in chromosome studies.

Main Methods:

• Development and application of single-cell Hi-C technology.
• Genome-wide statistical analysis.
• Structural modeling of single-copy X chromosomes.

Main Results:

• Individual chromosomes exhibit stable domain organization at the megabase scale.
• Significant cell-to-cell variability exists in chromosome structures at larger scales.
• Active gene domains are consistently found at the boundaries of chromosome territories, irrespective of larger-scale structural variations.

Conclusions:

• Chromosomal conformation is modular, underpinning dynamic chromosome structure.
• This dynamic structure is probabilistically linked to genome activity patterns.
• Single-cell Hi-C provides unprecedented resolution for studying chromosome organization and function.