title: Role of CtBP in transcriptional repression by the Drosophila giant protein.
abstract: The giant protein is a short-range transcriptional repressor that refines the expression pattern of gap and pair-rule genes in the Drosophila blastoderm embryo. Short-range repressors including knirps, Krüppel, and snail utilize the CtBP cofactor for repression, but it is not known whether a functional interaction with CtBP is a general property of all short-range repressors. We studied giant repression activity in a CtBP mutant and find that this cofactor is required for giant repression of some, but not all, genes. While targets of giant such as the even-skipped stripe 2 enhancer and a synthetic lacZ reporter show clear derepression in the CtBP mutant, another giant target, the hunchback gene, is expressed normally. A more complex situation is seen with regulation of the Krüppel gene, in which one enhancer is repressed by giant in a CtBP-dependent manner, while another is repressed in a CtBP-independent manner. These results demonstrate that giant can repress both via CtBP-dependent and CtBP-independent pathways, and that promoter context is critical for determining giant-CtBP functional interaction. To initiate mechanistic studies of the giant repression activity, we have identified a minimal repression domain within giant that encompasses residues 89-205, including an evolutionarily conserved region bearing a putative CtBP binding motif.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319, USA.
authors.forename: B
authors.initials: B
authors.lastname: Strunk
authors.forename: P
authors.initials: P
authors.lastname: Struffi
authors.forename: K
authors.initials: K
authors.lastname: Wright
authors.forename: B
authors.initials: B
authors.lastname: Pabst
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.forename: D N
authors.initials: DN
authors.lastname: Arnosti
mesh_terms: D000429:Alcohol Oxidoreductases; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D017403:In Situ Hybridization; D007763:Lac Operon; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D019076:Transgenes
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; C118475:gt protein, Drosophila; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein