Cross-linker mediated compaction and local morphologies in a model chromosome

Area of Science:

• Biophysics
• Polymer Physics
• Computational Biology

Background:

• Chromatin forms highly folded chromosome structures through interactions between DNA and associated proteins.
• Understanding the physical mechanisms of chromatin folding is crucial for comprehending genome organization and function.

Purpose of the Study:

• To investigate the folding transition of chromatin using a self-avoiding polymer model with cross-linking protein binders.
• To characterize the nature of the folding transition and the associated changes in polymer morphology.

Main Methods:

• Utilizing molecular dynamics simulations to model chromatin as a polymer.
• Employing a mean-field description to analyze the polymer-mediated interactions and folding behavior.
• Analyzing polymer size distributions, cross-linker cluster behavior, and local chain morphologies.

Main Results:

• Demonstrated the continuous nature of the chromatin folding transition, evidenced by unimodal polymer size distributions.
• Observed large fluctuations in chromatin size and cross-linker clusters at the transition point, along with critical slowing down.
• Identified distinct local chain morphologies, including topological loops and zippering, which vary with the folding phase.

Conclusions:

• The study provides explicit evidence for a continuous folding transition in a polymer model of chromatin.
• Protein binders play a key role in mediating polymer attraction and inducing folding.
• The transition is characterized by critical phenomena and a shift in dominant chain topologies from loops to zippering as the polymer folds.