title: Integration of Orthogonal Signaling by the Notch and Dpp Pathways in Drosophila.
abstract: The transcription factor Suppressor of Hairless and its coactivator, the Notch intracellular domain, are polyglutamine (pQ)-rich factors that target enhancer elements and interact with other locally bound pQ-rich factors. To understand the functional repertoire of such enhancers, we identify conserved regulatory belts with binding sites for the pQ-rich effectors of both Notch and BMP/Dpp signaling, and the pQ-deficient tissue selectors Apterous (Ap), Scalloped (Sd), and Vestigial (Vg). We find that the densest such binding site cluster in the genome is located in the BMP-inducible nab locus, a homolog of the vertebrate transcriptional cofactors NAB1/NAB2 We report three major findings. First, we find that this nab regulatory belt is a novel enhancer driving dorsal wing margin expression in regions of peak phosphorylated Mad in wing imaginal discs. Second, we show that Ap is developmentally required to license the nab dorsal wing margin enhancer (DWME) to read out Notch and Dpp signaling in the dorsal compartment. Third, we find that the nab DWME is embedded in a complex of intronic enhancers, including a wing quadrant enhancer, a proximal wing disc enhancer, and a larval brain enhancer. This enhancer complex coordinates global nab expression via both tissue-specific activation and interenhancer silencing. We suggest that DWME integration of BMP signaling maintains nab expression in proliferating margin descendants that have divided away from Notch-Delta boundary signaling. As such, uniform expression of genes like nab and vestigial in proliferating compartments would typically require both boundary and nonboundary lineage-specific enhancers.
authors.affiliation: Department of Biology, University of Iowa, Iowa City, Iowa 52242-1324.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stroebele
authors.affiliation: Department of Biology, University of Iowa, Iowa City, Iowa 52242-1324 albert-erives@uiowa.edu.
authors.forename: Albert
authors.identifier: 0000-0001-7107-5518
authors.initials: A
authors.lastname: Erives
mesh_terms: D000818:Animals; D001665:Binding Sites; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D007438:Introns; D059372:Nucleotide Motifs; D038081:Organogenesis / Q000235:genetics; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D037941:Silencer Elements, Transcriptional; D014921:Wings, Animal
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; C490626:NAB protein, Drosophila; D051880:Receptors, Notch; D012097:Repressor Proteins; C064196:dpp protein, Drosophila
keywords: Apterous; Dpp/BMP; Notch; Su(H); developmental genetics; imaginal disc patterning; nab; pQ signal integration; polyglutamine