ArticlePloS one2014
An integrated model of transcription factor diffusion shows the importance of intersegmental transfer and quaternary protein structure for target site finding.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
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- Modulating binding affinity, specificity, and configurations by multivalent interactions.Biophysical journal · 2022Article
- Emergent correlations in gene expression dynamics as footprints of resource competition.The European physical journal. E, Soft matter · 2021Article
- Discrete-state stochastic kinetic models for target DNA search by proteins: Theory and experimental applications.Biophysical chemistry · 2021Review
- Transient binding and jumping dynamics of p53 along DNA revealed by sub-millisecond resolved single-molecule fluorescence tracking.Scientific reports · 2020Article
- How p53 Molecules Solve the Target DNA Search Problem: A Review.International journal of molecular sciences · 2020Review
- Towards mapping the 3D genome through high speed single-molecule tracking of functional transcription factors in single living cells.Methods (San Diego, Calif.) · 2020Article
- Modelling and measuring intracellular competition for finite resources during gene expression.Journal of the Royal Society, Interface · 2019Article
- Intrinsically disordered domain of tumor suppressor p53 facilitates target search by ultrafast transfer between different DNA strands.Nucleic acids research · 2018Article
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- Processive searching ability varies among members of the gap-filling DNA polymerase X family.The Journal of biological chemistry · 2017Article
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- Tetrameric structure of the restriction DNA glycosylase R.PabI in complex with nonspecific double-stranded DNA.Scientific reports · 2016Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
We present a computational model of transcription factor motion that explains both the observed rapid target finding of transcription factors, and how this motion influences protein and genome structure. Using the Smoldyn software, we modelled transcription factor motion arising from a combination of unrestricted 3D diffusion in the nucleoplasm, sliding along the DNA filament, and transferring directly between filament sections by intersegmental transfer. This presents a fine-grain picture of the way in which transcription factors find their targets two orders of magnitude faster than 3D diffusion alone allows. Eukaryotic genomes contain sections of nucleosome free regions (NFRs) around the promoters; our model shows that the presence and size of these NFRs can be explained as their acting as antennas on which transcription factors slide to reach their targets. Additionally, our model shows that intersegmental transfer may have shaped the quaternary structure of transcription factors: sequence specific DNA binding proteins are unusually enriched in dimers and tetramers, perhaps because these allow intersegmental transfer, which accelerates target site finding. Finally, our model shows that a 'hopping' motion can emerge from 3D diffusion on small scales. This explains the apparently long sliding lengths that have been observed for some DNA binding proteins observed in vitro. Together, these results suggest that transcription factor diffusion dynamics help drive the evolution of protein and genome structure.
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