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Finding the Balance: Repression of Plant Gene Expression

寻找平衡：植物基因表达的抑制

基本信息

批准号：
BB/T001194/1
负责人：
Brendan Davies
金额：
$ 82.01万
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FT001194%2F1
关键词：
Finding Balance Repression Plant Gene

项目摘要

All life critically depends on the ability of organisms to set the expression levels of each of their genes. Textbook models claim that gene regulation is controlled by transcription factors (TFs); proteins that bind specific regions of the genome to 'turn on' or 'turn off' expression of target genes. The TFs provide specificity, identifying the correct genes to regulate, but they recruit other proteins to actually set the levels of gene expression. Many TFs turn off gene expression by recruiting proteins known as corepressors. Corepressors cannot bind DNA, but, once brought to a target by a specific TF, they can shut down expression of that target gene. More recent studies reject this simplistic model, in favour of a more nuanced model involving a regulated balance between activation and repression, to deliver the appropriate expression levels. Paradoxically then, in animals, repressive factors have been found to be part of complexes required to both repress and activate. An important class of animal and plant corepressors is the GRO/TUP1 family. The major group of these corepressors in plants is called TPL/TPR. TPL/TPRs are involved in multiple diverse plant processes and are absolutely fundamental to normal growth and development. Despite the fact that these regulators are so critical, their mode of action is poorly understood, with many open questions.There is accumulating evidence that plant TPL/TPR proteins inactivate gene expression as part of a larger complex containing histone deacetylase (HDAC) proteins. HDACs modify the chromatin structure of the target gene, rendering it inactive. In animals, HDACs are also associated with repression complexes, the most abundant of which is the nucleosome remodelling and deacetylase complex (NuRD). Currently, no such complex is known in plants. Some, but not all, of the core components of animal NuRDs are present in plant genomes and we recently identified homologues of animal NuRD components as TPL/TPR interaction partners. This raises the intriguing possibility that TPL/TPRs, which are so essential for normal plant function, repress transcription as part of a currently unknown plant NuRD-like complex. Such a complex would necessarily differ from those found in animals, because plants lack homologues of some of the core animal regulatory complex components. One aim of this proposal is therefore to isolate and characterise the first plant TPL/TPR-HDAC complex, both to understand how it controls gene expression and to compare it with the distinct, but analogous animal complexes. Using either newly identified components of the plant TPL/TPR-HDAC complex, or previously identified candidate components, we will then go on to use molecular genetics to investigate their role in gene expression.The balance model of transcriptional regulation is supported by the association of the animal NuRD-complex with both repressed and active genes. This model also provides a potential explanation for some perplexing results in plants. Our final aim is therefore to investigate whether these complexes are involved in both activation and repression in plants. By taking a global view of DNA-binding and gene expression, we will be able to identify the genomic regions that are associated with TPL/TPR corepressors and/or HDAC and to compare this to a genome-wide map of transcriptional activity. This powerful approach will allow us to quantify the genome association with TPL/TPR alone, HDAC alone and both together. We can then assign DNA association to a transcriptional status (activated or repressed) and, in some cases, compare this to the histone acetylation status of the gene.This project will provide a mechanistic framework for establishing a balance between repression and activation in plants that could be manipulated to alter plant development and responses. It will also reveal whether the novel plant regulatory complexes are involved in both repression and activation of gene expression.

所有的生命都依赖于生物体设定每个基因表达水平的能力。教科书模型声称，基因调控是由转录因子（TF）控制的;转录因子是一种结合基因组特定区域以“打开”或“关闭”靶基因表达的蛋白质。TF提供特异性，识别正确的基因进行调节，但它们招募其他蛋白质来实际设定基因表达水平。许多转铁蛋白通过募集被称为辅阻遏物的蛋白质来关闭基因表达。辅抑制因子不能结合DNA，但是，一旦被特定TF带到靶点，它们就可以关闭该靶基因的表达。最近的研究拒绝了这种简单化的模型，支持一种更微妙的模型，涉及激活和抑制之间的调节平衡，以提供适当的表达水平。奇怪的是，在动物中，压抑因子被发现是压抑和激活所需的复合物的一部分。一类重要的动物和植物辅阻遏物是GRO/TUP 1家族。这些辅阻遏物在植物中的主要组被称为TPL/TPR。TPL/TPR参与多种不同的植物过程，对正常生长和发育至关重要。尽管事实上，这些调节剂是如此关键，他们的行动模式是知之甚少，有许多悬而未决的questions.There是越来越多的证据表明，植物TPL/TPR蛋白作为一个更大的复合物的一部分，包含组蛋白脱乙酰酶（HDAC）蛋白的基因表达调控。HDAC修饰靶基因的染色质结构，使其失活。在动物中，HDAC也与阻遏复合物相关，其中最丰富的是核小体重塑和脱乙酰酶复合物（NuRD）。目前，在植物中还没有发现这样的复合物。一些，但不是全部，动物NuRD的核心成分存在于植物基因组中，我们最近确定了同源的动物NuRD组件TPL/TPR相互作用的合作伙伴。这提出了一个有趣的可能性，TPL/TPRs，这是如此重要的正常植物功能，抑制转录的一部分，目前未知的植物NuRD样复合物。这种复合物必然不同于动物中发现的复合物，因为植物缺乏某些核心动物调节复合物成分的同源物。因此，该提议的一个目的是分离和鉴定第一种植物TPL/TPR-HDAC复合物，以了解它如何控制基因表达，并将其与不同但类似的动物复合物进行比较。无论是新发现的植物TPL/TPR-HDAC复合物的组成部分，或以前确定的候选成分，我们将继续使用分子遗传学研究它们在基因expression.The转录调控的平衡模型的作用支持的协会的动物NuRD复合物与抑制和活性基因。这个模型也为植物中一些令人困惑的结果提供了一个潜在的解释。因此，我们的最终目的是研究这些复合物是否参与植物中的激活和阻遏。通过从整体上观察DNA结合和基因表达，我们将能够识别与TPL/TPR辅阻遏物和/或HDAC相关的基因组区域，并将其与全基因组转录活性图谱进行比较。这种强大的方法将使我们能够量化与TPL/TPR单独，HDAC单独和两者一起的基因组关联。然后，我们可以将DNA关联分配到转录状态（激活或抑制），并在某些情况下，将其与基因的组蛋白乙酰化状态进行比较。该项目将提供一个机制框架，用于在植物中建立抑制和激活之间的平衡，可以操纵该平衡来改变植物的发育和反应。它还将揭示新的植物调控复合物是否参与基因表达的抑制和激活。