MOLECULAR MECHANISM OF POLYHOMEOTIC ACTIVATION BY ENGRAILED

The Drosophila Engrailed homeoprotein has been shown to activate direc tly a Polycomb-group gene, polyhomeotic, during embryogenesis. The mol ecular mechanism involved in this activation has been studied. Two dif ferent types of Engrailed-binding fragments have been detected within the polyhomeotic locus. The P1 and D1 fragments contain several 'TTAAT TGCAT' motifs, whereas the D2 fragment contains a long 'TAAT' stretch to which multiple copies of Engrailed bind cooperatively. Another home odomain-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), a s well as Extradenticle, are necessary to obtain activation by Engrail ed. In vivo, we have also shown that normal polyhomeotic expression de pends on extradenticle expression, Moreover, in the absence of Extrade nticle, overexpression of Engrailed protein represses polyhomeotic exp ression.