Auxentric - a hormone-based mechanism to control chromatin state

所有细胞的命运，无论是单细胞的还是多细胞生物体的一部分，都是它们所表达的基因的函数。在多细胞生物体的发育过程中，激素等可移动分子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模式方面发挥重要作用，例如侧根、幼叶和雌蕊(雌性生殖器官)。在经典的生长素信号传递机制中，生长素分子促进特定蛋白质之间的相互作用，从而导致基因表达抑制物的崩溃。生长素还被证实可以通过控制生长素转运蛋白的局部化来影响自身的运输。虽然这些生长素信号传递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途径来解释生长素在其中发挥作用的众多过程。我们最近描述了由生长素反应因子ETTIN介导的另一种生长素信号通路，它在器官发育的极性建立过程中发挥着特别重要的作用。这种新的生长素信号传递机制(这里称为‘辅助’机制)与已建立的生长素信号传递过程有根本的不同，因为它涉及激素分子对ETTIN-转录因子(TF)复合体的直接影响，而不涉及蛋白质的降解。有趣的是，我们的初步数据表明，这种效应会导致染色质状态的变化，其机制类似于动物体内的甲状腺激素信号。在这个方案中，我们将揭示生长素通过调节其在含ETTIN的复合体中的作用来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。除了这一特定的机制之外，Auxentric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，这项工作将引入一种新的基于基因表达的植物激素感知机制，并在染色质水平上得出生长素动态和基因调控之间前所未有的联系。

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.