Auxentric - a hormone-based mechanism to control chromatin state

所有细胞的命运，无论是单细胞还是多细胞生物的一部分，都是它们表达的基因的功能。在多细胞生物的发育过程中，移动的分子如激素通过控制基因表达来调节细胞命运。植物激素生长素是最早被研究的激素之一，查尔斯达尔文和他的儿子弗朗西斯在19世纪80年代研究了生长素对光调节植物生长（向光性）的影响。然而，直到20世纪30年代，生长素分子才被分离出来，其分子结构被确定为吲哚-3-乙酸（IAA）。在植物中，生长素在启动器官形成和在特定组织类型中形成器官中起着重要作用，例如侧根，幼叶和雌蕊群（雌性生殖器官）。在经典的生长素信号传导机制中，生长素分子促进特定蛋白质之间的相互作用，从而导致基因表达的阻遏物的破坏。它也已被确定，生长素可以影响自己的运输，通过控制生长素转运蛋白的定位。虽然这些生长素信号传导机制可以解释生长素作用的许多过程，但可能存在其他转录信号传导途径来解释生长素发挥作用的众多过程。我们最近描述了另一种生长素信号通路介导的生长素反应因子，ETTIN，这在器官发育的极性建立过程中起着特别重要的作用。这种新型的生长素信号传导机制（这里称为“Auxentric”机制）与已建立的生长素信号传导过程有根本不同，因为它涉及激素分子对ETTIN-转录因子（TF）复合物的直接影响，而不涉及蛋白质降解。有趣的是，我们的初步数据表明，这种效应导致染色质状态的变化，其机制类似于动物中的甲状腺激素信号传导。在这个提议中，我们将揭示生长素介导其对含ETTIN的复合物的作用以控制基因表达的机制。此外，我们还将揭示所涉及的蛋白质和激素成分的生物物理和结构特征。除了这种特定的机制之外，植物中心可能对激素调节植物生长和发育的替代机制的存在具有深远的影响。因此，这里提出的工作将介绍一种新的基因表达为基础的机制，激素在植物中的感知，并绘制前所未有的生长素动态和基因调控之间的联系在染色质水平。

The fate of all cells, whether unicellular or part of a multicellular organism, is a function of the genes they express. During the development of multicellular organisms, mobile molecules such as hormones regulate cell fate by controlling gene expression. The plant hormone auxin was one of the first hormones to be studied and the effect of auxin on light-regulated plant growth (phototropism) was investigated by Charles Darwin and his son Francis in the 1880s. It was, however, not until the 1930s that the auxin molecule was isolated and its molecular structure determined as indole 3-acetic acid (IAA). In plants, auxin plays an essential role in initiating organ formation and in patterning the organs in specific tissue types, for example, lateral roots, young leaves and the gynoecium (the female reproductive organ). In the classical auxin-signalling mechanism, the auxin molecule promotes the interaction between specific proteins thereby causing the breakdown of repressors of gene expression. It has also been established that auxin can influence its own transport by controlling the localisation of auxin transporters. Although these mechanisms of auxin signalling can explain many processes of auxin action, other transcriptional signalling pathways are likely to exist to account for the multitude of processes in which auxin plays a role. We have recently described an alternative auxin-signalling pathway mediated by the auxin response factor, ETTIN, which plays a particularly important role during the establishment of polarity in organ development. This novel auxin-signalling mechanism (referred to here as the 'Auxentric' mechanism) is fundamentally different from established processes of auxin signalling as it involves a direct effect of the hormone molecule on ETTIN-transcription factor (TF) complexes without the involvement of protein degradation. Interestingly, our preliminary data suggest that this effect leads to changes in chromatin states in a mechanism similar to thyroid hormone signalling in animals. In this proposal, we will reveal the mechanism by which auxin mediates its effect on ETTIN-containing complexes to control gene expression. We will, moreover, unravel the biophysical and structural characteristics of the protein and hormonal components involved. Above and beyond this specific mechanism, Auxentric may have far-reaching implications for the existence of alternative mechanisms by which hormones regulate plant growth and development. The work proposed here will thus introduce a novel gene expression-based mechanism of hormone perception in plants and draw unprecedented links between auxin dynamics and gene regulation at the chromatin level.