Drosophila Goosecoid requires a conserved heptapeptide for repression of paired-class homeoprotein activators.
Goosecoid (Gsc) is a homeodomain protein expressed in the organizer region of vertebrate embryos. Its Drosophila homologue, D-Gsc, has been implicated in the formation of the Stomatogastric Nervous System. Although there are no apparent similarities between the phenotypes of mutations in the gsc gene in flies and mice, all known Gsc proteins can rescue dorsoanterior structures in ventralized Xenopus embryos. We describe how D-Gsc behaves as a transcriptional repressor in Drosophila cells, acting through specific palindromic HD binding sites (P3K). D-Gsc is a 'passive repressor' of activator homeoproteins binding to the same sites and an 'active repressor' of activators binding to distinct sites. In addition, D-Gsc is able to strongly repress transcription activated by Paired-class homeoproteins through P3K, via specific protein-protein interactions in what we define as 'interactive repression'. This form of repression requires the short conserved GEH/eh-1 domain, also present in the Engrailed repressor. Although the GEH/eh-1 domain is necessary for rescue of UV-ventralized Xenopus embryos, it is dispensable for ectopic induction of Xlim-1 expression, demonstrating that this domain is not required for all Gsc functions in vivo. Interactive repression may represent specific interactions among Prd-class homeoproteins, several of which act early during development of invertebrate and vertebrate embryos.
Mailhos
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C
Laboratory of Molecular Genetics, Howard Hughes Medical Institute, Rockefeller University, New York, USA.
André
S
S
Mollereau
B
B
Goriely
A
A
Hemmati-Brivanlou
A
A
Desplan
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019281:Dimerization; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D014982:Xenopus laevis
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051956:Goosecoid Protein; C497991:Gsc protein, Drosophila; D018398:Homeodomain Proteins; D019476:Insect Proteins; C489937:PRRX1 protein, Xenopus; C489936:Prrx1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C489935:prd protein, Drosophila; D004247:DNA