Goosecoid

Transcriptional Regulation

The three maternal systems (anterior-posterior [bicoid]; terminal [torso]; and dorsoventral control the early expression of Goosecoid: the GSC stripe never appears in bicoid mutants; the stripe is shifted anteriorly in torso mutants, while the ventral repression of the stripe is abolished in dorsal mutants (Goriely, 1996).

An effect on the early stripe of Goosecoid expression is observed in sloppy-paired, orthodenticle, tailless and decapentaplegic mutants. Both slp and otd affect Gsc in a similar way: the early stripe of Gsc appears normally but at the end of the cellularization stage, there is no reinforcement of its expression and it is prematurely lost. dpp is necessary either to bring about Gsc repression in the dorsal-most region of the embryo, while tll is required to promote Gsc expression in the lateral region, or to prevent its repression by the dorsoventral patterning system (Goriely, 1996).

Targets of Activity

Goosecoid (Gsc) is a homeodomain protein expressed in the organizer region of vertebrate embryos. 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. Drosophila Gsc behaves as a transcriptional repressor in Drosophila cells, acting through specific palindromic HD binding sites (P3K) that serve to bind homeodomain proteins (such as Gsc, Bicoid and Orthodenticle) that possess a lysine (K) residue at position 50 of their homodomains. Such P3K sites have the structure TAAT CCG ATTA (Mailhos, 1998).

Gsc is a 'passive repressor' of activator homeoproteins binding to the same sites and an 'active repressor' of activators binding to distinct sites. As a passive repressor, Gsc can repress transcription by Goosecoid itself, Orthodenticle (Otd) or Bicoid (Bcd). Gsc behaves as a passive repressor when acting on a reporter containing a single copy of the monomeric Bcd binding site, TAATCCC, through which Bcd can drive reporter expression. Gsc behaves as an active repressor on a reporter construct that contains three copies of the glucocorticoid response element inserted near a P3K site. In its capacity as an active repressor, Gsc might work by contacting the transcriptional machinery directly or via a general cofactor, and thus block transcription irrespective of the activator. Alternatively, Gsc could interact with the activator, either directly or indirectly through a cofactor, and thus block the effect of that particular activator (in this case the glucocorticoid receptor) (Mailhos, 1998).

Gsc is able to strongly repress transcription activated by Paired-class homeoproteins through P3K, via specific protein-protein interactions in what is defined as 'interactive repression'. This form of repression requires the short conserved GEH/eh-1 domain, also present in the Engrailed repressor. The GEH (Goosecoid Engrailed Homology) domain in Engrailed is present in addition to a 55 amino acid long alanine rich domain which also serves to repress transcription. 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 (dimerization) among Prd-class homeoproteins, several of which act early during development of invertebrate and vertebrate embryos (Mailhos, 1998).

Protein Interactions

Surprisingly small peptide motifs can confer critical biological functions. One example is the WRPW tetrapeptide present in the Hairy family of transcriptional repressors, that mediates recruitment of the Groucho (Gro) corepressor to target promoters. Engrailed (En) is another repressor that requires association with Gro for its function. En lacks a WRPW motif; instead, it contains another short conserved sequence, the En homology region 1 (eh1)/GEH motif, that is likely to play a role in tethering Gro to the promoter. A repressor domain from the Goosecoid (Gsc) developmental regulator is characterized that includes an eh1/GEH-like motif. This motif is found within the N-terminal half of the protein. The motif is 17 amino acids long and includes a 7-amino-acid core and ten flanking residues that are partly conserved among Gsc proteins. The flanking residues do not show significant similarity to the equivalent region of other eh1/GEH-containing proteins. Interestingly, a Phe residue in the core motif distinguishes the eh1/GEH motif from a related sequence known as the octapeptide, which is present in several paired-domain and homeodomain proteins. This domain (GscR) mediates efficient repression in Drosophila blastoderm embryos and repression by GscR requires Gro function. GscR and Gro interact in vitro, and the eh1/GEH motif is necessary and sufficient for the interaction and for in vivo repression. Because WRPW- and eh1/GEH-like motifs are present in different proteins and in many organisms, the results suggest that interactions between short peptides and Gro represent a widespread mechanism of repression. Finally, whether Gro is part of a stable multiprotein complex in the nucleus was investigated. These results indicate that Gro does not form stable associations with other proteins but that it may be able to assemble into homomultimeric complexes (Jimenez, 1999).

Home page: The Interactive Fly © 1997 Thomas B. Brody, Ph.D.

The Interactive Fly resides on the
Society for Developmental Biology's Web server.