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A Family of Transcriptional Co-repressors Controlling Multiple Processes in Plants

控制植物多个过程的转录辅阻遏物家族

基本信息

批准号：
BB/H018190/1
负责人：
Brendan Davies
金额：
$ 50.8万
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：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FH018190%2F1
关键词：
Family Transcriptional Co repressors Controlling

项目摘要

Living organisms need to turn expression of their genes on and off in response to their environment. Transcription factors bind to specific DNA sequences and control whether genes are activated or repressed. Turning off gene expression is not simply the absence of activation: actively shutting down expression of target genes is of vital importance. For example, in this proposal we will look at two cases where repressing target genes is required for essential plant processes. In one example, we will investigate the role of repression in hormone signalling and in the other we will look at the role of repression in maintaining the pool of undifferentiated cells at the growing tip of the shoot (the meristem) that is essential for plants to modulate their development in response to age and environment. Transcription factors repress gene expression using a class of proteins called transcriptional co-repressors. These proteins cannot bind DNA and must interact with transcription factors to be recruited to the regulatory regions of genes. Target gene specificity is contributed by the transcription factor and the repressive capacity is provided by the co-repressor. We identified the first members of a small family of plant co-repressors that here we call the TTW family. There are five TTW proteins in the model plant Arabidopsis. Others have shown that this family is required as a central part of the signalling mechanism for the plant hormone auxin. The ability of each cell to perceive its auxin environment and to regulate expression of its genes in response to that environment plays a huge part in shaping the plant and allowing it to function. Understanding how auxin levels are translated into instructions to turn genes on and off has been one of the major scientific achievements of the last 5 years. We now know that one of the key players in this signalling process is able to shut down gene expression by recruiting members of the TTW family. The TTW family is therefore already linked directly to two distinct processes that are central to plant life: meristem maintenance and auxin signalling. We have new data that indicate that the influence of the TTW family is much wider than this. Our evidence shows that just one member of the TTW family helps a minimum of 110 different transcription factors to repress target genes. It also implicates the TTW family in another phytohormone signalling pathway; suggesting that the remarkable organisational similarities between the jasmonic acid and auxin signalling pathways extend to a common use of this class of co-repressors. Given that many aspects of gene regulation appear to converge on this small family of proteins it is important that we understand how they work. To this end we propose three objectives that address the following questions: 1. Is the TTW family of co-repressors required to enact the repressive function in the jasmonic acid signalling pathway, as it is in the auxin signalling pathway? 2. Can we use the connection between the TTW corepressors and meristem maintenance to understand the mode of action of the TTW co-repressors? 3. Can we define the full extent of the interactions between the TTW proteins and plant transcription factors so that we can define exactly what allows any transcription factor to recruit a TTW co-repressor? The first question allows us to understand more about a vital hormone signalling pathway and reveals a remarkable evolutionary similarity between the way in which different proteins become organised in a similar way. The second question, explains the link between meristem maintenance and the TTW proteins, and shows how the TTW proteins actively shut down gene expression. The final question will produce a community resource to catalogue TTW - transcription factor interactions and should also help us to define the rules that determine which transcription factors interact with which co-repressors.

生物体需要根据环境调节基因表达的开启和关闭。转录因子结合到特定的DNA序列并控制基因是被激活还是被抑制。关闭基因表达不仅仅是缺乏激活：主动关闭目标基因的表达是至关重要的。例如，在本提案中，我们将研究两种情况，其中抑制靶基因是必需的植物过程。在一个例子中，我们将研究抑制在激素信号传导中的作用，在另一个例子中，我们将研究抑制在维持茎尖（分生组织）未分化细胞库中的作用，这对于植物调节其发育以响应年龄和环境至关重要。转录因子利用一类称为转录辅抑制因子的蛋白质来抑制基因表达。这些蛋白质不能结合DNA，必须与转录因子相互作用才能被招募到基因的调控区域。靶基因特异性由转录因子提供，抑制能力由共同抑制因子提供。我们确定了植物共同抑制因子小家族的第一批成员，我们称之为TTW家族。模式植物拟南芥中有5种TTW蛋白。其他研究表明，这个家族是植物激素生长素信号传导机制的核心部分。每个细胞感知其生长素环境的能力，以及根据环境调节其基因表达的能力，在植物的形成和发挥作用方面起着重要作用。了解生长素水平如何转化为基因开启和关闭的指令是过去5年的主要科学成就之一。我们现在知道，这个信号传导过程中的一个关键角色能够通过招募TTW家族成员来关闭基因表达。因此，TTW家族已经与植物生命的两个不同的核心过程直接相关：分生组织维持和生长素信号传导。我们有新的数据表明，TTW家族的影响要比这广泛得多。我们的证据表明，仅仅TTW家族的一个成员就可以帮助至少110种不同的转录因子来抑制靶基因。这也暗示TTW家族参与了另一种植物激素信号通路；这表明茉莉酸和生长素信号通路之间显著的组织相似性延伸到这类共阻遏物的共同使用。考虑到基因调控的许多方面似乎都集中在这个小的蛋白质家族上，我们了解它们是如何工作的就很重要了。为此，我们提出三个目标，以解决下列问题：TTW家族的共阻遏物是否需要在茉莉酸信号通路中发挥抑制作用，就像在生长素信号通路中一样？2. 我们能否利用TTW共阻遏子和分生系统维持之间的联系来理解TTW共阻遏子的作用模式？3. 我们能否定义TTW蛋白和植物转录因子之间相互作用的全部范围这样我们就能准确地定义是什么允许任何转录因子招募TTW协同抑制因子？第一个问题让我们对重要的激素信号传导途径有了更多的了解，并揭示了不同蛋白质以相似方式组织的方式之间的显著进化相似性。第二个问题解释了分生组织维持和TTW蛋白之间的联系，并展示了TTW蛋白如何主动关闭基因表达。最后一个问题将产生一个社区资源来编目TTW -转录因子相互作用，也应该帮助我们定义确定哪些转录因子与哪些共抑制因子相互作用的规则。