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PLoS Comput Biol. 2010 Nov 11;6(11):e1000989. doi: 10.1371/journal.pcbi.1000989.

Local gene regulation details a recognition code within the LacI transcriptional factor family.

Author information

1
Logic of Genomic Systems Laboratory, Spanish National Biotechnology Centre, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. fmcamas@gmail.com

Abstract

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.

PMID:
21085639
PMCID:
PMC2978694
DOI:
10.1371/journal.pcbi.1000989
[Indexed for MEDLINE]
Free PMC Article

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