title: The activity of the Drosophila morphogenetic protein Bicoid is inhibited by a domain located outside its homeodomain.
abstract: The Drosophila morphogenetic protein Bicoid (Bcd) is a homeodomain-containing activator that stimulates the expression of target genes during early embryonic development. We demonstrate that a small domain of Bcd located immediately N-terminally of the homeodomain represses its own activity in Drosophila cells. This domain, referred to as a self-inhibitory domain, works as an independent module that does not rely on any other sequences of Bcd and can repress the activity of heterologous activators. We further show that this domain of Bcd does not affect its properties of DNA binding or subcellular distribution. A Bcd derivative with point mutations in the self-inhibitory domain severely affects pattern formation and target gene expression in Drosophila embryos. We also provide evidence to suggest that the action of the self-inhibitory domain requires a Drosophila co-factor(s), other than CtBP or dSAP18. Our results suggest that proper action of Bcd as a transcriptional activator and molecular morphogen during embryonic development is dependent on the downregulation of its own activity through an interaction with a novel co-repressor(s) or complex(es).
authors.affiliation: Division of Developmental Biology, Children's Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Allen
authors.initials: A
authors.lastname: York
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: David J
authors.initials: DJ
authors.lastname: Forsthoefel
authors.forename: Vrushank
authors.initials: V
authors.lastname: Dave
authors.forename: Dechen
authors.initials: D
authors.lastname: Fu
authors.forename: Dongyi
authors.initials: D
authors.lastname: Zhang
authors.forename: Maria S
authors.initials: MS
authors.lastname: Corado
authors.forename: Stephen
authors.initials: S
authors.lastname: Small
authors.forename: Mark A
authors.initials: MA
authors.lastname: Seeger
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000429:Alcohol Oxidoreductases; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002352:Carrier Proteins; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; C056478:bcd protein, Drosophila; C407043:bicoid interacting protein 1, Drosophila; D004247:DNA; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein