title: Requirements for transcriptional repression and activation by Engrailed in Drosophila embryos.
abstract: Genetic analysis shows that Engrailed (En), a homeodomain-containing transcription factor, has both negative and positive targets. Negative regulation is expected from a factor that has a well-defined repressor domain but activation is harder to comprehend. We used VP16En, a form of En that had its repressor domain replaced by the activation domain of VP16, to show that En activates targets using two parallel routes, by repressing a repressor and by being a bona fide activator. We identified the intermediate repressor activity as being encoded by sloppy paired 1 and 2 and showed that bona fide activation is dramatically enhanced by Wingless signaling. Thus, En is a bifunctional transcription factor and the recruitment of additional cofactors presumably specifies which function prevails on an individual promoter. Extradenticle (Exd) is a cofactor thought to be required for activation by Hox proteins. However, in thoracic segments, Exd is required for repression (as well as activation) by En. This is consistent with in vitro results showing that Exd is involved in recognition of positive and negative targets. Moreover, we provide genetic evidence that, in abdominal segments, Ubx and Abd-A, two homeotic proteins not previously thought to participate in the segmentation cascade, are also involved in the repression of target genes by En. We suggest that, like Exd, Ubx and Abd-A could help En recognize target genes or activate the expression of factors that do so.
authors.affiliation: National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. calexan@nimr.mrc.ac.uk
authors.forename: Cyrille
authors.initials: C
authors.lastname: Alexandre
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vincent
mesh_terms: D000005:Abdomen / Q000196:embryology / Q000502:physiology; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013909:Thorax / Q000196:embryology / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D051155:Wnt1 Protein
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C063459:En protein, Drosophila; D018398:Homeodomain Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; C415845:VP16-E protein, Equine herpesvirus 1; D014764:Viral Proteins; D051155:Wnt1 Protein; C092937:ci protein, Drosophila; C083405:exd protein, Drosophila; C489935:prd protein, Drosophila; C074838:slp1 protein, Drosophila; C074622:wg protein, Drosophila; C066591:abd-A protein, Drosophila; C074839:slp2 protein, Drosophila