title: A composite motif of the Drosophila morphogenetic protein bicoid critical to transcription control.
abstract: Bicoid is a molecular morphogen-controlling embryonic patterning in Drosophila. It is a homeodomain-containing protein that activates specific target genes during early embryogenesis. Our recent studies have identified a domain of Bcd located outside its homeodomain and referred to as a self-inhibitory domain that can dramatically repress its own ability to activate transcription. Here we present evidence that the self-inhibitory function is evolutionarily conserved. A systematic analysis of this domain reveals a composite 10-amino acid motif with interdigitating residues that regulate Bcd activity in opposite manners. Mutations within the Bcd motif can exert their respective effects when the self-inhibitory domain is grafted to an entirely heterologous activator, but they do not affect DNA binding in vitro or subcellular localization of Bcd in cells. We further show that the self-inhibitory domain of Bcd can interact with Sin3A, a component of the histone deacetylase co-repressor complex. Our study suggests that the activity of Bcd is intricately controlled by multiple mechanisms involving the actions of co-repressor proteins.
authors.affiliation: Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Dechen
authors.initials: D
authors.lastname: Fu
authors.forename: Vrushank
authors.initials: V
authors.lastname: Dave
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D004330:Drosophila / Q000737:chemistry* / Q000196:embryology; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016296:Mutagenesis; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000737:chemistry* / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D018398:Homeodomain Proteins; D006877:Hydroxamic Acids; D015534:Trans-Activators; C056478:bcd protein, Drosophila; C012589:trichostatin A; D004247:DNA