Phase Separation and Correlated Motions in Motorized Genome.

Area of Science:

• Cell Biology
• Biophysics
• Genomics

Background:

• The spatial arrangement of the human genome within the cell nucleus is nonrandom.
• Phase separation is a proposed mechanism driving genome organization.
• The role of nonequilibrium activities in genome structure and dynamics remains largely unexplored.

Purpose of the Study:

• To investigate the impact of active, nonequilibrium forces on genome organization and dynamics.
• To explore how forces breaking detailed balance affect chromatin spatial localization.
• To understand the contribution of active processes to nuclear architecture.

Main Methods:

• Simulated the genome using an energy function parameterized with chromosome conformation capture (Hi-C) data.
• Incorporated active, nondirectional forces that disrupt detailed balance.
• Analyzed the spatial localization and correlations of genomic loci.

Main Results:

• Active forces significantly impact heterochromatin spatial localization.
• Active forces can drive heterochromatin to the nuclear envelope, counteracting passive interactions.
• Induced long-range spatial correlations among genomic loci beyond chromosome territories.
• The effect of active forces can be quantified using an effective temperature (fluctuation-dissipation ratio).

Conclusions:

• Nonequilibrium activities play a crucial role in shaping genome structure and dynamics.
• Active forces can lead to emergent collective phenomena in the cell nucleus.
• Understanding active processes is essential for comprehending nuclear organization.