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Published on: March 11, 2015
Diffusion, dimensionality, and noise in transcriptional regulation
Gasper Tkacik1, William Bialek
1Joseph Henry Laboratories of Physics, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Summary
Protein sliding along DNA enhances target searching but increases temporal correlations, largely canceling benefits for transcriptional regulation precision. This molecular diffusion has minimal impact on regulatory noise limits.
Area of Science:
- Biochemistry and Molecular Biology
- Biophysics
- Systems Biology
Background:
- Biochemical signaling precision is limited by molecular diffusion randomness.
- Proteins binding to DNA regulate transcription, and their search efficiency is crucial.
Purpose of the Study:
- To investigate the impact of one-dimensional DNA sliding on the precision of transcriptional regulation.
- To determine if DNA sliding reduces noise in protein-DNA binding and enhances signaling accuracy.
Main Methods:
- Theoretical modeling of molecular diffusion and binding kinetics.
- Analysis of one-dimensional sliding and three-dimensional diffusion effects.
- Incorporation of temporal correlations in diffusion models.
Main Results:
- While DNA sliding increases the effective target size for proteins, it also enhances temporal correlations in diffusion.
- These enhanced temporal correlations largely counteract the benefits of increased target searching.
- Simulations with realistic parameters show minimal improvement in regulatory precision due to sliding.
Conclusions:
- One-dimensional DNA sliding offers limited advantage in reducing noise for transcriptional regulation.
- The physical limits to the precision of gene regulation are not significantly improved by protein sliding along DNA.
- Understanding diffusion dynamics is key to comprehending the accuracy of biological signaling pathways.
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