Suchergebnisse

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 © 2010 Camas et al. ; This work was supported by a Spanish Government Formación de Profesorado Universitario fellowship (to F.M.C.), Ministerio de Ciencia e Innovación grant BFU2008-03632/BMC (to J.F.P), and Comunidad de Madrid grant CCG08-CSIC/SAL-3651 (to J.F.P). ; Peer Reviewed