Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences |
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Authors: | Berger Michael F Badis Gwenael Gehrke Andrew R Talukder Shaheynoor Philippakis Anthony A Peña-Castillo Lourdes Alleyne Trevis M Mnaimneh Sanie Botvinnik Olga B Chan Esther T Khalid Faiqua Zhang Wen Newburger Daniel Jaeger Savina A Morris Quaid D Bulyk Martha L Hughes Timothy R |
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Institution: | Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. |
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Abstract: | 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. |
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