Dynamical phase transition in models that couple chromatin folding with histone modifications

Area of Science:

• Epigenetics and Molecular Biology
• Computational Biology and Biophysics

Background:

• Heritable epigenetic states are established by histone modifications, influencing gene expression without DNA sequence changes.
• The link between chromatin conformational dynamics and epigenetic stability remains largely unexplored.

Purpose of the Study:

• To investigate dynamic fluctuations of histone modifications and nucleosome interactions using kinetic models.
• To explore the influence of chemical modifications and chromatin contacts on epigenetic stability.

Main Methods:

• Development of kinetic models incorporating chemical modification effects on chromatin structure.
• Utilizing stochastic simulations and analytical theory to analyze model dynamics.
• Validating model robustness against parameter and design variations.

Main Results:

• Discovery of distinct steady-state outcomes in different kinetic regimes, analogous to a dynamical phase transition.
• Identification of a robust transition occurring on biologically relevant timescales.
• Demonstration that chromatin viscoelasticity and gel-to-liquid transition timescales impact DNA-based dynamics.

Conclusions:

• Chromatin dynamics and epigenetic stability are intricately linked through a phase transition mechanism.
• The viscoelastic properties of chromatin play a critical role in regulating epigenetic states.
• Kinetic modeling provides insights into the mechanisms underlying epigenetic inheritance and gene regulation.