Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex.
Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex.
复制标题
DOI：
10.1242/dev.126.22.5137
复制
发表时间：
1999-11
期刊：
影响因子：
4.6
通讯作者：
H. Ryoo;T. Marty;F. Casares;M. Affolter;R. Mann
中科院分区：
文献类型：
--
作者：
H. Ryoo;T. Marty;F. Casares;M. Affolter;R. Mann
为了调节其靶基因，果蝇的Hox蛋白通常以异源二聚体的形式与外显异质结构域蛋白（EXD）结合。EXD要与DNA结合，必须在细胞核内，其核定位需要第三个同源结构域蛋白Homothorax （HTH）。本研究表明，HTH的一个保守的n端结构域在体外直接与EXD结合，并足以诱导EXD在体内的核定位。然而，突变HTH同源结构域中一个关键的DNA结合残基会取消其在体内的许多功能。HTH作为HTH/Hox/EXD三聚体复合物的一部分与DNA结合，我们发现该复合物对于激活天然Hox靶增强子至关重要。使用HTH的显性阴性形式，我们提供证据表明，类似的复合物在体内对几种Hox和exd介导的功能很重要。这些数据表明，Hox蛋白通常作为多蛋白复合物的一部分起作用，该复合物由HTH、Hox和EXD蛋白组成，与DNA结合。
To regulate their target genes, the Hox proteins of Drosophila often bind to DNA as heterodimers with the homeodomain protein Extradenticle (EXD). For EXD to bind DNA, it must be in the nucleus, and its nuclear localization requires a third homeodomain protein, Homothorax (HTH). Here we show that a conserved N-terminal domain of HTH directly binds to EXD in vitro, and is sufficient to induce the nuclear localization of EXD in vivo. However, mutating a key DNA binding residue in the HTH homeodomain abolishes many of its in vivo functions. HTH binds to DNA as part of a HTH/Hox/EXD trimeric complex, and we show that this complex is essential for the activation of a natural Hox target enhancer. Using a dominant negative form of HTH we provide evidence that similar complexes are important for several Hox- and exd-mediated functions in vivo. These data suggest that Hox proteins often function as part of a multiprotein complex, composed of HTH, Hox, and EXD proteins, bound to DNA.