title: Capicua DNA-binding sites are general response elements for RTK signaling in Drosophila.
abstract: RTK/Ras/MAPK signaling pathways play key functions in metazoan development, but how they control expression of downstream genes is not well understood. In Drosophila, it is generally assumed that most transcriptional responses to RTK signal activation depend on binding of Ets-family proteins to specific cis-acting sites in target enhancers. Here, we show that several Drosophila RTK pathways control expression of downstream genes through common octameric elements that are binding sites for the HMG-box factor Capicua, a transcriptional repressor that is downregulated by RTK signaling in different contexts. We show that Torso RTK-dependent regulation of terminal gap gene expression in the early embryo critically depends on Capicua octameric sites, and that binding of Capicua to these sites is essential for recruitment of the Groucho co-repressor to the huckebein enhancer in vivo. We then show that subsequent activation of the EGFR RTK pathway in the neuroectodermal region of the embryo controls dorsal-ventral gene expression by downregulating the Capicua protein, and that this control also depends on Capicua octameric motifs. Thus, a similar mechanism of RTK regulation operates during subdivision of the anterior-posterior and dorsal-ventral embryonic axes. We also find that identical DNA octamers mediate Capicua-dependent regulation of another EGFR target in the developing wing. Remarkably, a simple combination of activator-binding sites and Capicua motifs is sufficient to establish complex patterns of gene expression in response to both Torso and EGFR activation in different tissues. We conclude that Capicua octamers are general response elements for RTK signaling in Drosophila.
authors.affiliation: Institut de Biologia Molecular de Barcelona-CSIC, Parc Científic de Barcelona, Barcelona, Spain.
authors.forename: Leiore
authors.initials: L
authors.lastname: Ajuria
authors.forename: Claudia
authors.initials: C
authors.lastname: Nieva
authors.forename: Clint
authors.initials: C
authors.lastname: Winkler
authors.forename: Dennis
authors.initials: D
authors.lastname: Kuo
authors.forename: Núria
authors.initials: N
authors.lastname: Samper
authors.forename: María José
authors.initials: MJ
authors.lastname: Andreu
authors.forename: Aharon
authors.initials: A
authors.lastname: Helman
authors.forename: Sergio
authors.initials: S
authors.lastname: González-Crespo
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Paroush
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Courey
authors.forename: Gerardo
authors.initials: G
authors.lastname: Jiménez
mesh_terms: D000818:Animals; D001665:Binding Sites; D019521:Body Patterning; D004268:DNA-Binding Proteins; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D066246:ErbB Receptors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins / Q000235:genetics*; D020935:MAP Kinase Signaling System; D055503:Protein Multimerization; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D020218:Response Elements; D014921:Wings, Animal / Q000254:growth & development
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D024002:HMGB Proteins; D012097:Repressor Proteins; C404284:cic protein, Drosophila; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases