Zabet, Nicolae Radu and Foy, Robert and Adryan, Boris (2013) The Influence of Transcription Factor Competition on the Relationship between Occupancy and Affinity. PLoS ONE, 8 (9). e73714-e73714. DOI https://doi.org/10.1371/journal.pone.0073714
Zabet, Nicolae Radu and Foy, Robert and Adryan, Boris (2013) The Influence of Transcription Factor Competition on the Relationship between Occupancy and Affinity. PLoS ONE, 8 (9). e73714-e73714. DOI https://doi.org/10.1371/journal.pone.0073714
Zabet, Nicolae Radu and Foy, Robert and Adryan, Boris (2013) The Influence of Transcription Factor Competition on the Relationship between Occupancy and Affinity. PLoS ONE, 8 (9). e73714-e73714. DOI https://doi.org/10.1371/journal.pone.0073714
Abstract
Transcription factors (TFs) are proteins that bind to specific sites on the DNA and regulate gene activity. Identifying where TF molecules bind and how much time they spend on their target sites is key to understanding transcriptional regulation. It is usually assumed that the free energy of binding of a TF to the DNA (the affinity of the site) is highly correlated to the amount of time the TF remains bound (the occupancy of the site). However, knowing the binding energy is not sufficient to infer actual binding site occupancy. This mismatch between the occupancy predicted by the affinity and the observed occupancy may be caused by various factors, such as TF abundance, competition between TFs or the arrangement of the sites on the DNA. We investigated the relationship between the affinity of a TF for a set of binding sites and their occupancy. In particular, we considered the case of the transcription factor lac repressor (lacI) in E.coli, and performed stochastic simulations of the TF dynamics on the DNA for various combinations of lacI abundance and competing TFs that contribute to macromolecular crowding. We also investigated the relationship of site occupancy and the information content of position weight matrices (PWMs) used to represent binding sites. Our results showed that for medium and high affinity sites, TF competition does not play a significant role for genomic occupancy except in cases when the abundance of the TF is significantly increased, or when the PWM displays relatively low information content. Nevertheless, for medium and low affinity sites, an increase in TF abundance (for both cognate and non-cognate molecules) leads to an increase in occupancy at several sites. © 2013 Zabet et al.
Item Type: | Article |
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Uncontrolled Keywords: | Transcription Factors; DNA; Binding Sites |
Subjects: | Q Science > QC Physics Q Science > QH Natural history > QH426 Genetics |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 03 Nov 2015 14:38 |
Last Modified: | 30 Oct 2024 16:10 |
URI: | http://repository.essex.ac.uk/id/eprint/15114 |
Available files
Filename: journal.pone.0073714.pdf
Licence: Creative Commons: Attribution 3.0