Synthetic Priming of Transcriptional Memory

转录记忆的合成启动

• 批准号: EP/X025306/1
• 负责人: Clifford Harris
• 金额: $ 164.55万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX025306%2F1
• 关键词: Synthetic; Priming; Transcriptional; Memory

Plants have evolved the capacity to form 'memories' of pathogen attacks and other environmental stresses. These memories enable plants to mount a more vigorous response when the stress is encountered again. This effect, known as 'priming', has been observed across eukaryotes. Consistent with the ability of chromatin to carry information across mitotic and sometimes even meiotic divisions, recent research has linked chromatin changes to priming. However, it is not known how such chromatin changes produce a more effective response. Given that rapid deployment of transcriptional programs is critical for overcoming stresses, an attractive hypothesis is that priming re-sculpts chromatin to adopt a transcriptionally poised state that facilitates re-activation of stress-response genes. The proposed work will test this hypothesis for pathogen priming in Arabidopsis thaliana and will then seek to engineer plants to be primed for pathogen attack. In preliminary work, I have identified several pathogen primed genes, and I have established new tools that will allow me to address previously inaccessible questions regarding the mechanism by which chromatin confers transcriptional memory. In Aim 1, I will reveal the chromatin signature of priming (genomic techniques). In Aim 2, I will identify the factors acting downstream to perceive primed chromatin (quantitative proteomics). In Aim 3, I will discover the machinery required for transcriptional memory (forward and reverse genetics). In Aim 4, I will use the insights gained from Aims 1-3 to ask which chromatin features are necessary and sufficient to establish pathogen-primed transcriptional memory (epigenome engineering). This research, at the interface of epigenetics and immunity, will provide fundamental knowledge of the chromatin mechanisms that perpetuate active gene states, and explores the potential to instil primed 'memories' into naïve plants.

植物已经进化出对病原体攻击和其他环境压力形成“记忆”的能力。这些记忆使植物能够在再次遇到压力时做出更有力的反应。这种被称为“启动”的效应已经在真核生物中观察到。与染色质在有丝分裂甚至减数分裂中携带信息的能力一致，最近的研究将染色质的变化与启动联系在一起。然而，目前尚不清楚这种染色质变化如何产生更有效的反应。鉴于转录程序的快速部署对于克服压力至关重要，一个吸引人的假设是，启动重新塑造染色质，使其采用一种转录稳定的状态，从而促进应激反应基因的重新激活。这项拟议的工作将检验这一假说，以便在拟南芥中启动病原体，然后寻求改造植物，使其为病原体攻击做好准备。在初步工作中，我已经确定了几个病原体启动的基因，并建立了新的工具，将使我能够解决以前无法解决的问题，关于染色质赋予转录记忆的机制。在目标1中，我将揭示启动(基因组技术)的染色质特征。在目标2中，我将确定下游作用于感知启动染色质(定量蛋白质组学)的因素。在目标3中，我将发现转录记忆(正向和反向遗传学)所需的机制。在目标4中，我将使用从目标1-3获得的见解来询问哪些染色质特征是建立病原体启动的转录记忆(表观基因组工程)所必需的和充分的。这项研究介于表观遗传学和免疫学的交界处，将提供维持活跃基因状态的染色质机制的基础知识，并探索向幼稚植物灌输启动的“记忆”的可能性。

项目成果

Epigenetic processes in plant stress priming: Open questions and new approaches.

• DOI: 10.1016/j.pbi.2023.102432
• 发表时间: 2023-07
• 期刊: Current opinion in plant biology
• 影响因子: 9.5
• 作者: C. Harris;A. Amtmann;J. Ton