Hox specificity unique roles for cofactors and collaborators.
Hox specificity unique roles for cofactors and collaborators.
复制标题
DOI：
10.1016/s0070-2153(09)88003-4
复制
发表时间：
2009
影响因子：
--
通讯作者：
Joshi R
中科院分区：
文献类型：
--
作者：
Mann RS;Lelli KM;Joshi R
Hox 蛋白因在体内执行高度特异性的功能而闻名，但我们对这些令人着迷的蛋白质基因调控的分子机制的理解却滞后。本综述的前提是，了解任何转录因子的基因调控都需要剖析它们所作用的顺式调控元件。考虑到这一目标，我们回顾了有关 Hox 蛋白基因调控的概念和想法，并将其应用于已在文献中验证的直接调控的 Hox 顺式调控元件的精选列表。我们对这些元素内的 Hox 结合位点的分析提出了一些新出现的概括。我们区分了 Hox 辅因子（与 Hox 蛋白协同结合 DNA，从而帮助 DNA 结合位点选择的蛋白质）和 Hox 合作者（与 Hox 靶向顺式调控元件平行结合并决定基因调控的信号和强度的蛋白质）。最后，我们总结了通过检查 Hox-辅因子-DNA 复合物的五种 X 射线晶体结构得出的见解。总之，这些分析揭示了 Hox 蛋白如何发挥调节基因表达的巨大灵活性，或许可以解释为什么这些因素在动物界形态多样性的进化中发挥着核心作用。
Hox proteins are well known for executing highly specific functions in vivo, but our understanding of the molecular mechanisms underlying gene regulation by these fascinating proteins has lagged behind. The premise of this review is that an understanding of gene regulation — by any transcription factor—requires the dissection of the cis-regulatory elements that they act upon. With this goal in mind, we review the concepts and ideas regarding gene regulation by Hox proteins and apply them to a curated list of directly regulated Hox cis-regulatory elements that have been validated in the literature. Our analysis of the Hox-binding sites within these elements suggests several emerging generalizations. We distinguish between Hox cofactors, proteins that bind DNA cooperatively with Hox proteins and thereby help with DNA-binding site selection, and Hox collaborators, proteins that bind in parallel to Hox-targeted cis-regulatory elements and dictate the sign and strength of gene regulation. Finally, we summarize insights that come from examining five X-ray crystal structures of Hox-cofactor-DNA complexes. Together, these analyses reveal an enormous amount of flexibility into how Hox proteins function to regulate gene expression, perhaps providing an explanation for why these factors have been central players in the evolution of morphological diversity in the animal kingdom.