Yu Y, Li W, Su K, Yussa M, Han W, Perrimon N, Pick L
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Nature. 1997 Feb 6;385(6616):552-5. doi: 10.1038/385552a0.
Homeobox genes specify cell fate and positional identity in embryos throughout the animal kingdom. Paradoxically, although each has a specific function in vivo, the in vitro DNA-binding specificities of homeodomain proteins are overlapping and relatively weak. A current model is that homeodomain proteins interact with cofactors that increase specificity in vivo. Here we use a native binding site for the homeodomain protein Fushi tarazu (Ftz) to isolate Ftz-F1, a protein of the nuclear hormone-receptor superfamily and a new Ftz cofactor. Ftz and Ftz-F1 are present in a complex in Drosophila embryos. Ftz-F1 facilitates the binding of Ftz to DNA, allowing interactions with weak-affinity sites at concentrations of Ftz that alone bind only high-affinity sites. Embryos lacking Ftz-F1 display ftz-like pair-rule cuticular defects. This phenotype is a result of abnormal ftz function because it is expressed but fails to activate downstream target genes. Cooperative interaction between homeodomain proteins and cofactors of different classes may serve as a general mechanism to increase HOX protein specificity and to broaden the range of target sites they regulate.
同源异型基因在整个动物界的胚胎中决定细胞命运和位置身份。矛盾的是，尽管每个同源异型基因在体内都有特定功能，但同源结构域蛋白在体外的DNA结合特异性却相互重叠且相对较弱。当前的一种模型认为，同源结构域蛋白与能在体内增加特异性的辅因子相互作用。在这里，我们利用同源结构域蛋白腹缺口基因（Fushi tarazu，Ftz）的天然结合位点分离出了Ftz-F1，它是核激素受体超家族的一种蛋白，也是一种新的Ftz辅因子。Ftz和Ftz-F1在果蝇胚胎中以复合物形式存在。Ftz-F1促进Ftz与DNA的结合，使Ftz能在单独只能结合高亲和力位点的浓度下与低亲和力位点相互作用。缺乏Ftz-F1的胚胎表现出类似ftz的体节极性表皮缺陷。这种表型是ftz功能异常的结果，因为它虽有表达但无法激活下游靶基因。同源结构域蛋白与不同类别的辅因子之间的协同相互作用可能是增加HOX蛋白特异性以及扩大它们所调控的靶位点范围的一种普遍机制。
