title: Common binding by redundant group B Sox proteins is evolutionarily conserved in Drosophila.
abstract: BACKGROUND
  Group B Sox proteins are a highly conserved group of transcription factors that act extensively to coordinate nervous system development in higher metazoans while showing both co-expression and functional redundancy across a broad group of taxa. In Drosophila melanogaster, the two group B Sox proteins Dichaete and SoxNeuro show widespread common binding across the genome. While some instances of functional compensation have been observed in Drosophila, the function of common binding and the extent of its evolutionary conservation is not known.
  
  
  RESULTS
  We used DamID-seq to examine the genome-wide binding patterns of Dichaete and SoxNeuro in four species of Drosophila. Through a quantitative comparison of Dichaete binding, we evaluated the rate of binding site turnover across the genome as well as at specific functional sites. We also examined the presence of Sox motifs within binding intervals and the correlation between sequence conservation and binding conservation. To determine whether common binding between Dichaete and SoxNeuro is conserved, we performed a detailed analysis of the binding patterns of both factors in two species.
  
  
  CONCLUSIONS
  We find that, while the regulatory networks driven by Dichaete and SoxNeuro are largely conserved across the drosophilids studied, binding site turnover is widespread and correlated with phylogenetic distance. Nonetheless, binding is preferentially conserved at known cis-regulatory modules and core, independently verified binding sites. We observed the strongest binding conservation at sites that are commonly bound by Dichaete and SoxNeuro, suggesting that these sites are functionally important. Our analysis provides insights into the evolution of group B Sox function, highlighting the specific conservation of shared binding sites and suggesting alternative sources of neofunctionalisation between paralogous family members.
authors.affiliation: Department of Genetics and Cambridge Systems Biology Centre, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK. s.carl@gen.cam.ac.uk.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Carl
authors.affiliation: Department of Genetics and Cambridge Systems Biology Centre, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK. s.russell@gen.cam.ac.uk.
authors.forename: Steven
authors.initials: S
authors.lastname: Russell
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D055028:Comparative Genomic Hybridization; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks; D016678:Genome; D025341:Principal Component Analysis; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional; D055747:SOX Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: C103073:D protein, Drosophila; D029721:Drosophila Proteins; D055747:SOX Transcription Factors; C412366:SoxN protein, Drosophila