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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Main Authors: Camas, Francisco M., Alm, Eric J., Poyatos, Juan F.
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Public Library of Science 2011
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.
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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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