title: Evolved Repression Overcomes Enhancer Robustness.
abstract: Biological systems display extraordinary robustness. Robustness of transcriptional enhancers results mainly from clusters of binding sites for the same transcription factor, and it is not clear how robust enhancers can evolve loss of expression through point mutations. Here, we report the high-resolution functional dissection of a robust enhancer of the shavenbaby gene that has contributed to morphological evolution. We found that robustness is encoded by many binding sites for the transcriptional activator Arrowhead and that, during evolution, some of these activator sites were lost, weakening enhancer activity. Complete silencing of enhancer function, however, required evolution of a binding site for the spatially restricted potent repressor Abrupt. These findings illustrate that recruitment of repressor binding sites can overcome enhancer robustness and may minimize pleiotropic consequences of enhancer evolution. Recruitment of repression may be a general mode of evolution to break robust regulatory linkages.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA. Electronic address: pregere@janelia.hhmi.org.
authors.forename: Ella
authors.initials: E
authors.lastname: Preger-Ben Noon
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Fred P
authors.initials: FP
authors.lastname: Davis
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA. Electronic address: sternd@janelia.hhmi.org.
authors.forename: David L
authors.initials: DL
authors.lastname: Stern
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D063185:Epigenetic Repression; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D017344:Genes, Insect; D014644:Genetic Variation; D060850:LIM-Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C108601:Awh protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D060850:LIM-Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C531978:ab protein, Drosophila; C089512:ovo protein, Drosophila
keywords: enhancer evolution; morphology; repression; robustness; transcription