title: Essential roles of Da transactivation domains in neurogenesis and in E(spl)-mediated repression.
abstract: E proteins are a special class of basic helix-loop-helix (bHLH) proteins that heterodimerize with many bHLH activators to regulate developmental decisions, such as myogenesis and neurogenesis. Daughterless (Da) is the sole E protein in Drosophila and is ubiquitously expressed. We have characterized two transcription activation domains (TADs) in Da, called activation domain 1 (AD1) and loop-helix (LH), and have evaluated their roles in promoting peripheral neurogenesis. In this context, Da heterodimerizes with proneural proteins, such as Scute (Sc), which is dynamically expressed and also contributes a TAD. We found that either one of the Da TADs in the Da/Sc complex is sufficient to promote neurogenesis, whereas the Sc TAD is incapable of doing so. Besides its transcriptional activation role, the Da AD1 domain serves as an interaction platform for E(spl) proteins, bHLH-Orange family repressors which antagonize Da/Sc function. We show that the E(spl) Orange domain is needed for this interaction and strongly contributes to the antiproneural activity of E(spl) proteins. We present a mechanistic model on the interplay of these bHLH factors in the context of neural fate assignment.
authors.affiliation: Institute of Molecular Biology & Biotechnology, Foundation for Research & Technology Hellas, and Department of Biology, University of Crete, Heraklion, Crete, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Zarifi
authors.forename: Marianthi
authors.initials: M
authors.lastname: Kiparaki
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Koumbanakis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Giagtzoglou
authors.forename: Evanthia
authors.initials: E
authors.lastname: Zacharioudaki
authors.forename: Anastasios
authors.initials: A
authors.lastname: Alexiadis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Livadaras
authors.forename: Christos
authors.initials: C
authors.lastname: Delidakis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007313:Insecta; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000235:genetics*; D010957:Plasmids; D058105:Polymerization; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C090080:Da protein, Drosophila; C121960:E(spl)m7-HLH protein, Drosophila; C089197:sc protein, Drosophila