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Related Experiment Video

Updated: Jun 7, 2025

3D Multicolor DNA FISH Tool to Study Nuclear Architecture in Human Primary Cells

3D Multicolor DNA FISH Tool to Study Nuclear Architecture in Human Primary Cells

Published on: January 25, 2020

The chromosome folding problem and how cells solve it.

Job Dekker¹, Leonid A Mirny²

¹Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.

|November 15, 2024

Summary

Cells use conserved mechanisms like molecular motors and DNA topology to fold their genomes. These processes ensure genome replication, compaction, and segregation, and are later adapted for gene regulation.

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Area of Science:

Genomics
Molecular Biology
Cell Biology

Background:

All cells must organize their genome into a compact, functional state.
Chromosome folding is essential for fundamental cellular processes like replication and segregation.

Purpose of the Study:

To elucidate the conserved mechanisms underlying genome folding.
To explain the diversity of chromosome conformations across life and cell cycles.

Main Methods:

Analysis of conserved mechanisms including homotypic affinity, loop extrusion by molecular motors, and topological constraints.
Examination of tethering to sub-nuclear structures.

Main Results:

Chromosome folding arises from integrated activities of multiple conserved mechanisms.
Spatial partitioning of active and inactive genomic regions is driven by homotypic affinity.
Loop extrusion by molecular motors is a key folding mechanism.
Supercoiling, entanglements, and sub-nuclear tethering provide additional folding constraints.

Conclusions:

Diverse chromosome conformations result from differential regulation of basic folding mechanisms.
Primary functions of early chromosome folding were genome replication, compaction, and segregation.
Folding mechanisms were later co-opted for roles such as long-range gene regulation.