Multiple LacI-mediated loops revealed by Bayesian statistics and tethered particle motion
| Autor: | Jan-Willem van de Meent, Stephanie Johnson, Rob Phillips, Chris H. Wiggins, Martin Lindén |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Biophysics
FOS: Physical sciences Computational biology Lac repressor Bayesian inference chemistry.chemical_compound 03 medical and health sciences Motion 0302 clinical medicine Bacterial transcription Genetics Transcriptional regulation Lac Repressors Physics - Biological Physics Hidden Markov model 030304 developmental biology Physics 0303 health sciences Computational Biology Biomolecules (q-bio.BM) Bayes Theorem DNA Biofysik Markov Chains Bayesian statistics Kinetics chemistry Tethered particle motion Quantitative Biology - Biomolecules Biological Physics (physics.bio-ph) Physics - Data Analysis Statistics and Probability FOS: Biological sciences Nucleic Acid Conformation Artifacts 030217 neurology & neurosurgery Data Analysis Statistics and Probability (physics.data-an) |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | The bacterial transcription factor LacI loops DNA by binding to two separate locations on the DNA simultaneously. Despite being one of the best-studied model systems for transcriptional regulation, the number and conformations of loop structures accessible to LacI remain unclear, though the importance of multiple co-existing loops has been implicated in interactions between LacI and other cellular regulators of gene expression. To probe this issue, we have developed a new analysis method for tethered particle motion, a versatile and commonly-used in vitro single-molecule technique. Our method, vbTPM, performs variational Bayesian inference in hidden Markov models. It learns the number of distinct states (i.e., DNA-protein conformations) directly from tethered particle motion data with better resolution than existing methods, while easily correcting for common experimental artifacts. Studying short (roughly 100 bp) LacI-mediated loops, we provide evidence for three distinct loop structures, more than previously reported in single-molecule studies. Moreover, our results confirm that changes in LacI conformation and DNA binding topology both contribute to the repertoire of LacI-mediated loops formed in vitro, and provide qualitatively new input for models of looping and transcriptional regulation. We expect vbTPM to be broadly useful for probing complex protein-nucleic acid interactions. Comment: 34 pages, 25 figures, including Supporting information. To appear in Nucleic Acids Research. Accompanying open-source software: http://sourceforge.net/projects/vbtpm/ |
| Databáze: | OpenAIRE |
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