Spatial effects on the speed and reliability of protein–DNA search
Strong experimental and theoretical evidence shows that transcription factors (TFs) and other specific DNA-binding proteins find their sites using a two-mode search: alternating between three-dimensional (3D) diffusion through the cell and one-dimensional (1D) sliding along the DNA. We show that, du...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Oxford University Press (OUP)
2012
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| Online Access: | http://hdl.handle.net/1721.1/73060 https://orcid.org/0000-0002-0785-5410 |
| _version_ | 1811098206525718528 |
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| author | Wunderlich, Zeba Mirny, Leonid A. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Wunderlich, Zeba Mirny, Leonid A. |
| author_sort | Wunderlich, Zeba |
| collection | MIT |
| description | Strong experimental and theoretical evidence shows that transcription factors (TFs) and other specific DNA-binding proteins find their sites using a two-mode search: alternating between three-dimensional (3D) diffusion through the cell and one-dimensional (1D) sliding along the DNA. We show that, due to the 1D component of the search process, the search time of a TF can depend on the initial position of the TF. We formalize this effect by discriminating between two types of searches: global and local. Using analytical calculations and simulations, we estimate how close a TF and binding site need to be to make a local search likely. We then use our model to interpret the wide range of experimental measurements of this parameter. We also show that local and global searches differ significantly in average search time and the variability of search time. These results lead to a number of biological implications, including suggestions of how prokaryotes achieve rapid gene regulation and the relationship between the search mechanism and noise in gene expression. Lastly, we propose a number of experiments to verify the existence and quantify the extent of spatial effects on the TF search process in prokaryotes. |
| first_indexed | 2024-09-23T17:11:16Z |
| format | Article |
| id | mit-1721.1/73060 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:11:16Z |
| publishDate | 2012 |
| publisher | Oxford University Press (OUP) |
| record_format | dspace |
| spelling | mit-1721.1/730602022-10-03T11:01:55Z Spatial effects on the speed and reliability of protein–DNA search Wunderlich, Zeba Mirny, Leonid A. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Physics Massachusetts Institute of Technology. School of Engineering Mirny, Leonid A. Strong experimental and theoretical evidence shows that transcription factors (TFs) and other specific DNA-binding proteins find their sites using a two-mode search: alternating between three-dimensional (3D) diffusion through the cell and one-dimensional (1D) sliding along the DNA. We show that, due to the 1D component of the search process, the search time of a TF can depend on the initial position of the TF. We formalize this effect by discriminating between two types of searches: global and local. Using analytical calculations and simulations, we estimate how close a TF and binding site need to be to make a local search likely. We then use our model to interpret the wide range of experimental measurements of this parameter. We also show that local and global searches differ significantly in average search time and the variability of search time. These results lead to a number of biological implications, including suggestions of how prokaryotes achieve rapid gene regulation and the relationship between the search mechanism and noise in gene expression. Lastly, we propose a number of experiments to verify the existence and quantify the extent of spatial effects on the TF search process in prokaryotes. 2012-09-20T13:07:14Z 2012-09-20T13:07:14Z 2008-05 2008-03 Article http://purl.org/eprint/type/JournalArticle 0305-1048 1362-4962 http://hdl.handle.net/1721.1/73060 Wunderlich, Z., and L. A. Mirny. “Spatial Effects on the Speed and Reliability of protein-DNA Search.” Nucleic Acids Research 36.11 (2008): 3570–3578. https://orcid.org/0000-0002-0785-5410 en_US http://dx.doi.org/10.1093/nar/gkn173 Nucleic Acids Research Creative Commons Attribution Non-Commercial http://creativecommons.org/licenses/by-nc/2.5 application/pdf Oxford University Press (OUP) Oxford |
| spellingShingle | Wunderlich, Zeba Mirny, Leonid A. Spatial effects on the speed and reliability of protein–DNA search |
| title | Spatial effects on the speed and reliability of protein–DNA search |
| title_full | Spatial effects on the speed and reliability of protein–DNA search |
| title_fullStr | Spatial effects on the speed and reliability of protein–DNA search |
| title_full_unstemmed | Spatial effects on the speed and reliability of protein–DNA search |
| title_short | Spatial effects on the speed and reliability of protein–DNA search |
| title_sort | spatial effects on the speed and reliability of protein dna search |
| url | http://hdl.handle.net/1721.1/73060 https://orcid.org/0000-0002-0785-5410 |
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