Molecular mechanism of polyhomeotic activation by Engrailed.
The Drosophila Engrailed homeoprotein has been shown to activate directly a Polycomb-group gene, polyhomeotic, during embryogenesis. The molecular mechanism involved in this activation has been studied. Two different types of Engrailed-binding fragments have been detected within the polyhomeotic locus. The P1 and D1 fragments contain several 'TTAATTGCAT' motifs, whereas the D2 fragment contains a long 'TAAT' stretch to which multiple copies of Engrailed bind cooperatively. Another homeodomain-containing protein, Extradenticle, establishes protein-protein interactions with Engrailed on the D2 fragment. We have shown by CAT assays that both types of Engrailed-binding sites (P1 or D1 and D2), as well as Extradenticle, are necessary to obtain activation by Engrailed. In vivo, we have also shown that normal polyhomeotic expression depends on extradenticle expression. Moreover, in the absence of Extradenticle, overexpression of Engrailed protein represses polyhomeotic expression.
Serrano
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N
Département de Biologie du Développement, Institut Jacques Monod. 2, place Jussieu, 75251 Paris Cédex 05, France. serrano@cgl.ucsf.edu
Maschat
F
F
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000235:genetics*; D063150:Polycomb Repressive Complex 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C063459:En protein, Drosophila; D018398:Homeodomain Proteins; D019476:Insect Proteins; D009698:Nucleoproteins; D014157:Transcription Factors; C083405:exd protein, Drosophila; C072820:ph-d protein, Drosophila; D063150:Polycomb Repressive Complex 1