Function of photobodies in Arabidopsis photoreceptor signaling

摘要 如何在功能上和动态上组织细胞核是理解基本原理的核心问题 细胞过程，包括基因组组织和转录调控。两种动物的间期 植物核含有形态不同的、无膜结合的亚核细胞器，这些细胞器是 统称为核物体。尽管越来越多的证据表明，核物体在 在基因调控中的作用，以及核体的形态和组成的变化 与疾病相关的核体生物发生的确切功能和调控机制 转录调控仍然知之甚少。一个主要的挑战是缺乏遗传模型。 描述核体在通过细胞信号进行转录调控的背景下的功能。这个 PI实验室的长期目标是利用光体--拟南芥的一个亚核结构域 包含光感受器光敏色素B(PHYB)--作为阐明核功能的遗传模型 小体在细胞信号和转录调控中。目前的数据支持核心假设，即 光体是转录调节点，其中PHYB招募转录因子来调节其 稳定性以及它们的靶基因的活性。这一假说是建立在 Pi先前对光体所需两个新的光信号成分的分子遗传学研究 生物发生，命名为HMR和RCB，以及初步结果显示直接招募个人 基因与光体的关系。在这里，PI计划通过以下具体目标来检验这一中心假设：(1) 确定光体在调节转录因子稳定性中的功能；(2)确定其作用 RCB在光体功能和生物发生中的作用；(3)确定空间基因组的机制 按光体组织。这项拟议的研究具有创新性，因为它利用了光体和 拟南芥中的光感受器信号作为研究核神秘机制的遗传模型 组织--核体在转录调控和基因组中的功能和生物发生 组织。PI的实验室开创了光体模型的发展，发现了新的信号 由多个正向遗传筛选形成光体所需的组分，并建立了 光体和转录调控之间的机械联系。这项拟议的研究具有重要意义 因为预计它将发现将核体生物发生与调节 转录因子的稳定性及其靶基因的活性。因为基本原则是 基因调控在动物、真菌和植物界都是保守的，更好地理解 拟南芥中光体的功能有助于理解进化上保守的 真核生物基因组组织和转录调控的原理，从而最终将 提高对人类疾病中核组织调控不当的认识。

Abstract How the cell nucleus is functionally and dynamically organized is a central question to understanding basic cellular processes, including genome organization and transcriptional regulation. The interphase of both animal and plant nuclei contain morphologically distinct, non-membrane bound subnuclear organelles that are collectively called nuclear bodies. Although accumulating evidence suggests that nuclear bodies play important roles in gene regulation, and changes in the morphology and constitution of nuclear bodies have been associated with diseases, the precise function and regulatory mechanism of nuclear body biogenesis in transcriptional regulation remain poorly understood. One major challenge has been the lack of genetic models to delineate the functions of nuclear bodies in the context of transcriptional regulation by cell signaling. The long-term goal of the PI’s laboratory is to utilize the photobody – a subnuclear domain in Arabidopsis containing the photoreceptor phytochrome B (PHYB) – as a genetic model to elucidate the function of nuclear bodies in cell signaling and transcriptional regulation. The current data support the central hypothesis that photobodies are transcriptional regulatory foci wherein PHYB recruits transcription factors to regulate their stability as well as the activity of their target genes. This hypothesis has been formulated on the basis of the PI’s previous molecular genetic studies on two new light signaling components required for photobody biogenesis, named HMR and RCB, and on the preliminary results showing direct recruitment of individual genes to photobodies. Here the PI plans to test this central hypothesis by the following specific aims: (1) Determine the function of photobodies in regulating the stability of transcription factors; (2) Determine the role of RCB in the function and biogenesis of photobodies; (3) Determine the mechanism of spatial genome organization by photobodies. The proposed research is innovative, because it utilizes the photobody and photoreceptor signaling in Arabidopsis as a genetic model to investigate the enigmatic mechanisms of nuclear organization – the function and biogenesis of nuclear bodies in transcriptional regulation and genome organization. The PI’s laboratory pioneered the development of the photobody model, identified new signaling components required for photobody formation by multiple forward genetic screens, and established a mechanistic link between photobodies and transcriptional regulation. The proposed research is significant because it is expected to uncover novel mechanisms linking nuclear body biogenesis to the regulation of the stability of transcription factors as well as the activity of their target genes. Because the basic principles of gene regulation are conserved across the animal, fungal, and plant kingdoms, a better understanding of the function of photobodies in Arabidopsis will contribute to understanding of the evolutionarily conserved principles of genome organization and transcriptional regulation in eukaryotes and thereby will ultimately enhance our understanding of the misregulation of nuclear organization in human diseases.