title: Brinker requires two corepressors for maximal and versatile repression in Dpp signalling.
abstract: decapentaplegic (dpp) encodes a Drosophila transforming growth factor-beta homologue that functions as a morphogen in the developing embryo and in adult appendage formation. In the wing imaginal disc, a Dpp gradient governs patterning along the anteroposterior axis by inducing regional expression of diverse genes in a concentration-dependent manner. Recent studies show that responses to graded Dpp activity also require an input from a complementary and opposing gradient of Brinker (Brk), a transcriptional repressor protein encoded by a Dpp target gene. Here we show that Brk harbours a functional and transferable repression domain, through which it recruits the corepressors Groucho and CtBP. By analysing transcriptional outcomes arising from the genetic removal of these corepressors, and by ectopically expressing Brk variants in the embryo, we demonstrate that these corepressors are alternatively used by Brk for repressing some Dpp-responsive genes, whereas for repressing other distinct target genes they are not required. Our results show that Brk utilizes multiple means to repress its endogenous target genes, allowing repression of a multitude of complex Dpp target promoters.
authors.affiliation: Department of Biochemistry, The Hebrew University-Hadassah Medical School, PO Box 12272, Jerusalem 91120, Israel.
authors.forename: P
authors.initials: P
authors.lastname: Hasson
authors.forename: B
authors.initials: B
authors.lastname: Müller
authors.forename: K
authors.initials: K
authors.lastname: Basler
authors.forename: Z
authors.initials: Z
authors.lastname: Paroush
mesh_terms: D000429:Alcohol Oxidoreductases; D020816:Amino Acid Motifs; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology*; D046911:Macromolecular Substances; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009928:Organ Specificity; D010750:Phosphoproteins / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D014921:Wings, Animal / Q000196:embryology
chemical_list: D000429:Alcohol Oxidoreductases; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; C067777:Sxl protein, Drosophila; C118082:brk protein, Drosophila; C064196:dpp protein, Drosophila; C091023:gro protein, Drosophila; C095064:vg protein, Drosophila; C072962:bi protein, Drosophila; C096794:C-terminal binding protein