Conservation of transcription factor binding specificities across 600 million years of bilateria evolution
Kazuhiro R Nitta, Arttu Jolma, Yimeng Yin, Ekaterina Morgunova, Teemu Kivioja, Junaid Akhtar, Korneel Hens, Jarkko Toivonen, Bart Deplancke, Eileen E M Furlong, Jussi Taipale
Karolinska Institutet, Sweden; University of Helsinki, Finland; European Molecular Biology Laboratory, Germany; Swiss Federal Institute of Technology, Switzerland; Ecole Polytechnique Fédérale de Lausanne, Switzerland
Published March 17, 2015
Cite as eLife 2015;4:e04837
Abstract
Divergent morphology of species has largely been ascribed to genetic differences in the tissue-specific expression of proteins, which could be achieved by divergence in cis-regulatory elements or by altering the binding specificity of transcription factors (TFs). The relative importance of the latter has been difficult to assess, as previous systematic analyses of TF binding specificity have been performed using different methods in different species. To address this, we determined the binding specificities of 242 Drosophila TFs, and compared them to human and mouse data. This analysis revealed that TF binding specificities are highly conserved between Drosophila and mammals, and that for orthologous TFs, the similarity extends even to the level of very subtle dinucleotide binding preferences. The few human TFs with divergent specificities function in cell types not found in fruit flies, suggesting that evolution of TF specificities contributes to emergence of novel types of differentiated cells.
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