Synthetic Priming of Transcriptional Memory

植物已经进化出形成病原体攻击和其他环境压力“记忆”的能力。这些记忆使植物在再次遇到压力时能够做出更有力的反应。这种效应被称为“引发”，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变化与引发联系起来。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，一个有吸引力的假设是，引发重新塑造染色质，以采取转录平衡状态，促进应激反应基因的重新激活。拟议的工作将测试这一假设的病原体引发拟南芥，然后将寻求工程植物被引发病原体攻击。在初步工作中，我已经确定了几个病原体引发的基因，我已经建立了新的工具，使我能够解决以前无法解决的问题，染色质赋予转录记忆的机制。在目标1中，我将揭示引发的染色质特征（基因组技术）。在目标2中，我将确定下游作用的因素，以感知引发的染色质（定量蛋白质组学）。在目标3中，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，我将使用从目标1-3中获得的见解来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）是必要的和足够的。这项研究处于表观遗传学和免疫学的结合点，将提供有关维持活性基因状态的染色质机制的基础知识，并探索将启动“记忆”灌输到原始植物中的潜力。

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.