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.

植物已经进化出形成病原体攻击和其他环境胁迫的“记忆”的能力，这些记忆使植物在再次遇到胁迫时能够做出更强烈的反应，这种效应被称为“启动”，已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，最近的研究已将染色质变化与启动联系起来。然而，尚不清楚这种染色质变化如何产生更有效的效果。鉴于转录程序的快速部署对于克服压力至关重要，一个有吸引力的假设是启动重新塑造染色质以采取转录平衡状态，从而促进压力反应基因的重新激活。在拟南芥中进行病原体引发，然后寻求工程改造植物以应对病原体攻击。在初步工作中，我已经确定了几个病原体引发的基因，并且我已经建立了新的工具，使我能够解决以前的问题。关于染色质赋予转录记忆作用的机制的难以理解的问题在目标 1 中，我将揭示启动的染色质特征（基因组技术），在目标 2 中，我将确定感知启动染色质的下游因素（定量蛋白质组学）。目标 3，我将发现转录记忆所需的机制（正向和反向遗传学）。在目标 4 中，我将利用从目标中获得的见解。 1-3 询问哪些染色质特征对于建立病原体引发的转录记忆（表观基因组工程）是必要和充分的。这项研究在表观遗传学和免疫的界面上，将提供维持活性基因状态的染色质机制的基础知识，以及探索向幼稚植物灌输启动“记忆”的潜力。

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