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© Research
Publication : Cell

Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell - 27 Jun 2008

Berger MF, Badis G, Gehrke AR, Talukder S, Philippakis AA, Peña-Castillo L, Alleyne TM, Mnaimneh S, Botvinnik OB, Chan ET, Khalid F, Zhang W, Newburger D, Jaeger SA, Morris QD, Bulyk ML, Hughes TR.

Link to Pubmed [PMID] – 18585359

Cell. 2008 Jun 27;133(7):1266-76.

Most homeodomains are unique within a genome, yet many are highly conserved across vast evolutionary distances, implying strong selection on their precise DNA-binding specificities. We determined the binding preferences of the majority (168) of mouse homeodomains to all possible 8-base sequences, revealing rich and complex patterns of sequence specificity and showing that there are at least 65 distinct homeodomain DNA-binding activities. We developed a computational system that successfully predicts binding sites for homeodomain proteins as distant from mouse as Drosophila and C. elegans, and we infer full 8-mer binding profiles for the majority of known animal homeodomains. Our results provide an unprecedented level of resolution in the analysis of this simple domain structure and suggest that variation in sequence recognition may be a factor in its functional diversity and evolutionary success.