Protein-Protein Interactions Can Accelerate Transcription Factor Target Search on DNA
Aniruddha Nagarajan1,2, Sandeep Choubey1,2, Anatoly B Kolomeisky3,4,5,6
1The Institute of Mathematical Sciences , CIT Campus, Taramani, Chennai600113, India.
The Journal of Physical Chemistry Letters
|July 22, 2026
Summary
Transcription factors (TFs) binding to DNA is crucial for gene expression. We found that TF dimerization can significantly speed up the search for target DNA sites, enhancing gene regulation efficiency.
Area of Science:
- Molecular Biology
- Biophysics
- Systems Biology
Background:
- Transcription factors (TFs) initiate gene expression by binding to specific DNA promoter sites.
- Recent evidence suggests TFs form oligomers and phase-separated bodies through protein-protein interactions.
- The influence of these interactions on TF binding dynamics and target site recognition is not well understood.
Purpose of the Study:
- To quantitatively investigate the impact of TF dimerization on target searching dynamics on DNA.
- To elucidate how protein-protein interactions affect the kinetics of TF binding to DNA.
- To explore the role of dimerization in regulating gene expression efficiency.
Main Methods:
- Development of a discrete-state stochastic model to simulate TF target search.
- Analytical calculations and kinetic Monte Carlo simulations were employed.
- Analysis of TF association, dissociation, and sliding dynamics in the presence of dimerization.
Main Results:
- TF dimerization alters effective association, dissociation, and sliding dynamics, significantly changing target search kinetics.
- The collective behavior of TFs is highly dependent on the dominant search regime.
- Specific parameter regimes show that dimerization substantially accelerates target site localization, enhancing search efficiency.
Conclusions:
- TF dimerization can be a critical factor in regulating the efficiency of target site recognition on DNA.
- The findings provide physical and chemical explanations for the observed effects of dimerization.
- Modulating protein-protein interactions of TFs presents a potential strategy for controlling genetic information transfer.
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