title: Conservation of transcription factor binding specificities across 600 million years of bilateria evolution.
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.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kazuhiro R
authors.initials: KR
authors.lastname: Nitta
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arttu
authors.initials: A
authors.lastname: Jolma
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Morgunova
authors.affiliation: Genome-Scale Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Kivioja
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Junaid
authors.initials: J
authors.lastname: Akhtar
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland.
authors.forename: Korneel
authors.initials: K
authors.lastname: Hens
authors.affiliation: Department of Computer Science, University of Helsinki, Helsinki, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Toivonen
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Eileen E M
authors.initials: EE
authors.lastname: Furlong
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D004330:Drosophila; D020440:Gene Duplication; D006801:Humans; D051379:Mice; D010802:Phylogeny; D052156:SELEX Aptamer Technique; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors
keywords: D. melanogaster; DNA binding specificity; HT-SELEX; chromosomes; evolutionary biology; evolutionary conservation; genes; genomics; human; transcription factors