Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21122-7. doi: 10.1073/pnas.1114118109. Epub 2011 Dec 12.
Homeotic selector (Hox) proteins often bind DNA cooperatively with cofactors such as Extradenticle (Exd) and Homothorax (Hth) to achieve functional specificity in vivo. Previous studies identified the Hox YPWM motif as an important Exd interaction motif. Using a comparative approach, we characterize the contribution of this and additional conserved sequence motifs to the regulation of specific target genes for three Drosophila Hox proteins. We find that Sex combs reduced (Scr) uses a simple interaction mechanism, where a single tryptophan-containing motif is necessary for Exd-dependent DNA-binding and in vivo functions. Abdominal-A (AbdA) is more complex, using multiple conserved motifs in a context-dependent manner. Lastly, Ultrabithorax (Ubx) is the most flexible, in that it uses multiple conserved motifs that function in parallel to regulate target genes in vivo. We propose that using different binding mechanisms with the same cofactor may be one strategy to achieve functional specificity in vivo.
同源异形选择器（Hox）蛋白通常与 Extradenticle（Exd）和 Homothorax（Hth）等辅助因子协同结合 DNA，以在体内实现功能特异性。先前的研究确定了 Hox YPWM 基序是 Exd 相互作用的重要基序。我们采用比较方法，研究了该基序和其他保守序列基序对三种果蝇 Hox 蛋白特定靶基因调控的贡献。我们发现 Sex combs reduced（Scr）使用一种简单的相互作用机制，其中单个含色氨酸的基序对于 Exd 依赖性 DNA 结合和体内功能是必需的。Abdominal-A（AbdA）更为复杂，以依赖上下文的方式使用多个保守基序。最后，Ultrabithorax（Ubx）是最灵活的，因为它使用多个保守基序，这些基序以并行方式发挥作用，以在体内调节靶基因。我们提出，使用与相同辅助因子不同的结合机制可能是在体内实现功能特异性的一种策略。
