Serrano N, Maschat F
Département de Biologie du Développement, Institut Jacques Monod. 2, place Jussieu, 75251 Paris Cédex 05, France.
EMBO J. 1998 Jul 1;17(13):3704-13. doi: 10.1093/emboj/17.13.3704.
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.
已证明果蝇的Engrailed同源异型蛋白在胚胎发生过程中可直接激活一个多梳基因家族基因——多同源异型基因。对这种激活所涉及的分子机制进行了研究。在多同源异型基因座内检测到了两种不同类型的Engrailed结合片段。P1和D1片段含有几个“TTAATTGCAT”基序，而D2片段含有一段长的“TAAT”序列，Engrailed的多个拷贝可协同结合于此。另一种含同源异型结构域的蛋白——额外齿状蛋白，在D2片段上与Engrailed建立蛋白质-蛋白质相互作用。我们通过CAT分析表明，两种类型的Engrailed结合位点（P1或D1以及D2）以及额外齿状蛋白对于Engrailed激活都是必需的。在体内，我们还表明正常的多同源异型基因表达依赖于额外齿状蛋白的表达。此外，在没有额外齿状蛋白的情况下，Engrailed蛋白的过表达会抑制多同源异型基因的表达。
