Phase behaviour of DNA in presence of DNA-binding proteins

Abstract

To characterize the thermodynamical equilibrium of DNA chains interacting with a solution of non-specific binding proteins, a Flory-Huggins free energy model was implemented. We explored the dependence on DNA and protein concentrations of the DNA collapse. For physiologically relevant values of the DNA-protein affinity, this collapse gives rise to a biphasic regime with a dense and a dilute phase; the corresponding phase diagram was computed. Using an approach based on Hamiltonian paths, we show that the dense phase has either a molten globule or a crystalline structure, depending on the DNA bending rigidity, which is influenced by the ionic strength. These results are valid at the thermodynamical equilibrium and should therefore be consistent with many biological processes, whose characteristic timescales range typically from 1 ms to 10 s. Our model may thus be applied to biological phenomena that involve DNA-binding proteins, such as DNA condensation with crystalline order, which occurs in some bacteria to protect their chromosome from detrimental factors; or transcription initiation, which occurs in clusters called transcription factories that are reminiscent of the dense phase characterized in this study.

arXiv comment20 pages, 9 figures, accepted for publication at The Biophysical Journal

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• Phase separation of polymer-bound particles induced by loop-mediated 1D effective long-range interactions
• Cross-linker mediated compaction and local morphologies in a model chromosome
• A nonequilibrium strategy for fast target search on the genome
• Extension and dynamical phases in random walkers depositing and following chemical trails