Functional organization of the human 4D Nucleome

Area of Science:

• Genomics
• Cell Biology
• Systems Biology

Background:

• The 4D Nucleome (4DN) describes the dynamic 3D organization of the interphase nucleus.
• Understanding 4DN is crucial for linking genome structure, function, and phenotype.

Purpose of the Study:

• To analyze the human 4DN by integrating genome structure and function data.
• To develop a quantitative index for genomic topological stability.
• To explore correlations between genomic structure, function, and gene regulation.

Main Methods:

• Genome-wide structure capture using chromosome conformation capture and 3D imaging.
• Genome-wide function analysis via RNA-sequencing.
• Development of a quantitative index for topological stability.
• Construction of genome-wide gene-level contact maps.
• Visualization of 4DN data using 2D phase planes.

Main Results:

• Structural features of genomic regions show persistent correlation with function over time.
• Gene-level contact maps identified potential coregulated and colocalized gene pairs, consistent with transcription factories.
• Periodicity in the relative movement of circadian clock genes was observed, entraining with their expression.

Conclusions:

• Genomic structure and function are persistently linked in the 4D Nucleome.
• The developed index and contact maps provide insights into gene regulation and organization.
• Dynamic spatial relationships of genes, like those in circadian modules, follow rhythmic patterns linked to their expression.