Bilateral BBSRC-SFI: Characterization of a novel Polycomb group protein complex and its effects on the plant epigenome

双边 BBSRC-SFI：新型 Polycomb 族蛋白复合物的表征及其对植物表观基因组的影响

• 批准号: BB/P008569/1
• 负责人: Justin Goodrich
• 金额: $ 61.93万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP008569%2F1
• 关键词: Bilateral; BBSRC; SFI; Characterization; novel

The DNA in our cells is packaged on proteins called histones. Recently it has become clear that the histone proteins can be modified in many different ways, for example by addition of methyl groups, and that this can affect the activity of genes nearby. These changes in the histone proteins - often termed epigenetic marks - are important not only because they affect gene activity, but also because in some cases they are inherited through cell division. Intense research focus on the histone proteins has revealed that cells contain sophisticated machinery not only to "write" epigenetic marks, but also to read them, i.e. recognise and interpret them to produce an output such as turning a gene off. In addition, there are "erasers" that can remove specific marks and reverse their effects. One of the most important histone writers are the Polycomb group (PcG) proteins, which control many aspects of development in animals and plants and are thought to provide cells with a stable memory of important events. For example, in plants the PcG proteins help plant flower at the right time of year by giving cells a memory of whether or not winter has occurred. During winter the cold temperatures result in certain genes involved in flowering being switched off and the PcG proteins are important in making sure that cells "remember" to keep these genes off when temperatures increase during spring and summer. For a long time it was a complete mystery how PcG proteins caused these stable memories. In the last ten years there have been major advances. In particular, it has been found that a group of PcG proteins, called PRC2, act together as an enzyme which methylates a specific amino acid on one of the four histone proteins that package DNA. Furthermore, technical developments in sequencing mean that we can now identify which genes in an organism are modified in this way, and how this relates to their activity. Because PcG proteins control genes involved in many economically important traits (flowering, seed size, and the viability of hybrids for example) it is important to know how the activity of the PRC2 is regulated.The starting point for the present proposal was our discovery of several proteins, called ALP, which we found from genetic evidence which suggested that they act oppositely to the PcG and are involved in switching genes on. We later found, somewhat to our surprise, that the ALP proteins and the PRC2 PcG proteins act together in a large multiprotein complex. We think that when the ALP proteins associate with the PRC2 proteins they inhibit their activity so that the normal role of PcG in repressing gene activity is overcome. A further surprise was that the ALP1 protein turns out to be related to proteins called transposases which help parasitic elements called transposons to proliferate in plant and animal genomes. Because the ALP proteins are widely conserved in plants, including cereals, we think they could provide a useful tool to alter the epigenetic marks in plants and ultimately to modify useful agricultural traits. In order to do this, we need to know what effect ALP proteins have on PRC2 proteins, which genes they target, and what effects they have on the distribution of epigenetic marks over the genome. We have developed many of the genetic resources necessary to do this in our earlier work. We have also uncovered an unusual effect of ALP proteins on plants ability to perceive winter (the vernalization response) and wish to investigate whether this is a result of ALP proteins altering epigenetic marks at genes important for vernalization.We propose to conduct the research outlined in this application as a partnership between our laboratories at the University of Edinburgh and Trinity College Dublin, respectively. Our two groups have complementary research strengths and expertise and we believe that, as a team, we can successfully address questions that could not be answered by one group alone.

我们细胞中的 DNA 包装在称为组蛋白的蛋白质上。最近人们已经清楚，组蛋白可以通过多种不同的方式进行修饰，例如通过添加甲基，这可以影响附近基因的活性。组蛋白的这些变化（通常称为表观遗传标记）很重要，不仅因为它们影响基因活性，而且因为在某些情况下它们是通过细胞分裂遗传的。对组蛋白的深入研究表明，细胞含有复杂的机制，不仅可以“写入”表观遗传标记，还可以读取它们，即识别和解释它们以产生诸如关闭基因之类的输出。此外，还有“橡皮擦”可以去除特定标记并扭转其效果。最重要的组蛋白书写者之一是多梳族 (PcG) 蛋白，它控制着动物和植物发育的许多方面，并被认为可以为细胞提供重要事件的稳定记忆。例如，在植物中，PcG 蛋白可以让细胞记住冬天是否已经发生，从而帮助植物在一年中正确的时间开花。在冬季，寒冷的气温会导致某些与开花相关的基因被关闭，而 PcG 蛋白对于确保细胞在春季和夏季气温升高时“记住”关闭这些基因非常重要。长期以来，PcG 蛋白如何产生这些稳定的记忆一直是个谜。在过去的十年里，已经取得了重大进展。特别是，已经发现一组称为 PRC2 的 PcG 蛋白一起作为一种酶，将包装 DNA 的四种组蛋白之一上的特定氨基酸甲基化。此外，测序技术的发展意味着我们现在可以确定生物体中的哪些基因以这种方式被修饰，以及这与它们的活性有何关系。由于 PcG 蛋白控制涉及许多重要经济性状（例如开花、种子大小和杂种活力）的基因，因此了解 PRC2 的活性如何受到调节非常重要。本提案的出发点是我们发现我们从遗传证据中发现了几种称为 ALP 的蛋白质，这些证据表明它们的作用与 PcG 相反，并且参与基因的开启。后来我们发现，ALP 蛋白和 PRC2 PcG 蛋白在一个大型多蛋白复合物中共同作用，这让我们有些惊讶。我们认为，当 ALP 蛋白与 PRC2 蛋白结合时，它们会抑制其活性，从而克服了 PcG 抑制基因活性的正常作用。更令人惊讶的是，ALP1 蛋白与转座酶蛋白相关，转座酶有助于转座子寄生元件在植物和动物基因组中增殖。由于 ALP 蛋白在包括谷物在内的植物中广泛保守，我们认为它们可以提供一种有用的工具来改变植物的表观遗传标记，并最终改变有用的农业性状。为了做到这一点，我们需要知道 ALP 蛋白对 PRC2 蛋白有什么影响，它们靶向哪些基因，以及它们对基因组上表观遗传标记的分布有什么影响。在我们早期的工作中，我们已经开发了许多实现这一目标所需的遗传资源。我们还发现 ALP 蛋白对植物感知冬季的能力（春化反应）有一种不寻常的影响，并希望研究这是否是 ALP 蛋白改变对春化重要的基因表观遗传标记的结果。我们建议进行该应用程序是我们分别位于爱丁堡大学和都柏林三一学院的实验室之间的合作伙伴关系。我们的两个小组具有互补的研究优势和专业知识，我们相信，作为一个团队，我们可以成功解决仅靠一个小组无法回答的问题。

项目成果

CRISPR/Cas9-mediated restoration of Tamyb10 to create pre-harvest sprouting-resistant red wheat.

CRISPR/Cas9 介导的 Tamyb10 修复，创造出收获前抗发芽的红小麦。

• DOI: 10.1111/pbi.13981
• 发表时间: 2023-04
• 期刊: PLANT BIOTECHNOLOGY JOURNAL
• 影响因子: 13.8
• 作者: Zhu, Yiwang;Lin, Yarong;Fan, Yujin;Wang, Yiwei;Li, Pengfeng;Xiong, Jiang;He, Yuhan;Cheng, Shifeng;Ye, Xingguo;Wang, Feng;Goodrich, Justin;Zhu, Jian-Kang;Wang, Ke;Zhang, Cui-Jun
• 通讯作者: Zhang, Cui-Jun

The domesticated transposase ALP2 mediates formation of a novel Polycomb protein complex by direct interaction with MSI1, a core subunit of Polycomb Repressive Complex 2 (PRC2)

驯化转座酶 ALP2 通过与 Polycomb 抑制复合物 2 (PRC2) 的核心亚基 MSI1 直接相互作用介导新型 Polycomb 蛋白复合物的形成

• DOI: 10.1371/journal.pgen.1008681
• 发表时间: 2020
• 期刊: PLOS Genetics
• 影响因子: 4.5
• 作者: Velanis, Christos N.;Perera, Pumi;Thomson, Bennett;de Leau, Erica;Liang, Shih Chieh;Hartwig, Ben;Förderer, Alexander;Thornton, Harry;Arede, Pedro;Chen, Jiawen
• 通讯作者: Chen, Jiawen

Vernalization and Epigenetic Inheritance: A Game of Histones.

春化和表观遗传：组蛋白的游戏。

• DOI: 10.1016/j.cub.2017.10.048
• 发表时间: 2017
• 期刊: CB
• 作者: Velanis CN