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Visualization of DNA Compaction in Cyanobacteria by High-voltage Cryo-electron Tomography

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Published on: July 17, 2018

Chromosome Compaction by Active Loop Extrusion.

Anton Goloborodko¹, John F Marko², Leonid A Mirny³

¹Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts.

Biophysical Journal

|May 26, 2016

Summary

This summary is machine-generated.

Enzymatic machines called loop-extruding factors (LEFs) actively compact chromosomes by extruding chromatin loops. Their collective action creates dynamic loop arrays, explaining how human chromosomes achieve significant compaction.

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Area of Science:

Cell Biology
Molecular Biology
Biophysics

Background:

Mammalian chromosomes compact over 100-fold during cell division.
Compacted chromosomes feature arrays of stacked ∼100 kb loops.
The mechanism of active chromosome compaction remains unclear.

Purpose of the Study:

To test the hypothesis that loop-extruding factors (LEFs) actively compact chromosomes.
To model the process of loop extrusion and its effect on chromosome structure.
To understand how LEF properties influence chromosome compaction.

Main Methods:

Computational modeling and simulations.
Analytical solution of a mathematical model.
Comparison of model predictions with experimental data on human chromosomes.

Main Results:

A model of collective LEF action predicts dynamic loop arrays with two steady states: sparse and dense.
Human chromosomes operate near the dense steady state, characterized by stable loops and high compaction.
Model parameters matching experimental estimates quantitatively reproduce key features of compact human chromosomes.

Conclusions:

Active loop extrusion by LEFs is a sufficient mechanism for efficient chromosome compaction.
The abundance and properties of LEFs determine the macroscopic structure of the loop array.
This work elucidates a fundamental process in genome organization and cell division.