Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family
The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs) and nucleotides (NTs). This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. H...
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Public Library of Science
2011
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Online Access: | http://hdl.handle.net/1721.1/64754 https://orcid.org/0000-0001-8294-9364 |
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author | Camas, Francisco M. Alm, Eric J. Poyatos, Juan F. |
author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Camas, Francisco M. Alm, Eric J. Poyatos, Juan F. |
author_sort | Camas, Francisco M. |
collection | MIT |
description | The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs) and nucleotides (NTs). This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs). We searched for recognition patterns by introducing a new approach to phylogenetic footprinting, based on the pervasive presence of local regulation in prokaryotic transcriptional networks. We identified a set of specificity correlations –determined by two AAs of the TFs and two NTs in the binding sites– that is conserved
throughout a dominant subgroup within the family regardless of the evolutionary distance, and that act as a relatively consistent recognition code. The proposed rules are confirmed with data of previous experimental studies and by events of convergent evolution in the phylogenetic tree. The presence of a code emphasizes the stable structural context of the LacI family, while defining a precise blueprint to reprogram TF specificity with many practical applications. |
first_indexed | 2024-09-23T11:49:04Z |
format | Article |
id | mit-1721.1/64754 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T11:49:04Z |
publishDate | 2011 |
publisher | Public Library of Science |
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spelling | mit-1721.1/647542022-09-27T22:05:56Z Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family Camas, Francisco M. Alm, Eric J. Poyatos, Juan F. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Alm, Eric J. Alm, Eric J. The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs) and nucleotides (NTs). This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs). We searched for recognition patterns by introducing a new approach to phylogenetic footprinting, based on the pervasive presence of local regulation in prokaryotic transcriptional networks. We identified a set of specificity correlations –determined by two AAs of the TFs and two NTs in the binding sites– that is conserved throughout a dominant subgroup within the family regardless of the evolutionary distance, and that act as a relatively consistent recognition code. The proposed rules are confirmed with data of previous experimental studies and by events of convergent evolution in the phylogenetic tree. The presence of a code emphasizes the stable structural context of the LacI family, while defining a precise blueprint to reprogram TF specificity with many practical applications. Ministerio de Ciencia e Innovación, Spain (Formación de Profesorado Universitario fellowship) Ministerio de Ciencia e Innovación, Spain (grant BFU2008-03632/BMC) Madrid (Spain : Region) (grant CCG08-CSIC/SAL-3651) 2011-07-06T20:46:21Z 2011-07-06T20:46:21Z 2010-11 2010-05 Article http://purl.org/eprint/type/JournalArticle 1553-7358 1553-734X http://hdl.handle.net/1721.1/64754 Camas, Francisco M., Eric J. Alm, and Juan F. Poyatos. "Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family." PLoS Computational Biology 6(11): e1000989. https://orcid.org/0000-0001-8294-9364 en_US http://dx.doi.org/10.1371/journal.pcbi.1000989 PLoS Computational Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
spellingShingle | Camas, Francisco M. Alm, Eric J. Poyatos, Juan F. Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family |
title | Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family |
title_full | Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family |
title_fullStr | Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family |
title_full_unstemmed | Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family |
title_short | Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family |
title_sort | local gene regulation details a recognition code within the laci transcriptional factor family |
url | http://hdl.handle.net/1721.1/64754 https://orcid.org/0000-0001-8294-9364 |
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