Epigenetically stable hypomethylated plants to exploit epigenetic diversity

表观遗传稳定的低甲基化植物可利用表观遗传多样性

• 批准号: BB/W008866/1
• 负责人: Marco Catoni
• 金额: $ 71.11万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW008866%2F1
• 关键词: Epigenetically; stable; hypomethylated; plants; exploit

Epigenetics studies biological traits which are not dependent on changes in DNA sequence. In plants, many of these epigenetic changes are stable and are transmitted very efficiently from parent to offspring. Therefore, epigenetic variability represents an important source of biological variation, including traits potentially able to improve crop plants and develop sustainable agriculture. However, the main limitation of using epigenetic traits in agriculture is our inability to induce sufficient epigenetic diversity in plants without interfering with critical developmental pathways. My working hypothesis is that these epigenetic negative effects on plant development could be associated with the epigenetic alteration of a single gene called IBM1. In the model plant Arabidopsis thaliana, if the IBM1 sequence loses DNA methylation (a strong epigenetic mark) in a crucial region located in one of its introns, a shorter non-functional transcript is produced. Since a functional IBM1 is essential to maintain correct epigenetic regulation at many genes, the lack of IBM1 function allows the accumulation of epigenetic defects and reduces plant fitness across generations. In stable Arabidopsis plant lines with identical genome sequence but different degrees of reduction in DNA methylation, I observed that IBM1 gene was always inherited in its methylated version, suggesting that the removal of DNA methylation at this locus has a negative impact on plant fitness. To test this hypothesis I will investigate the relationship between plant epigenetic stability, decrease of fitness, and different epigenetic regulation of the IBM1 gene. I will also test if the artificial generation of an IBM1 allele insensitive to DNA methylation can be a suitable approach to avoid the negative effects associated to the generation of epigenetic variability.Obviously, the possibility to generate new epigenetic variation in plants without affecting their fitness will generate a larger impact if directly explored into crops, where new traits could be exploited into breeding programs. In this direction my preliminary investigation suggests that the epigenetic regulation of IBM1 is conserved in wheat. Therefore, in this project I will also transform wheat with an IBM1 allele insensitive to epigenetic regulation, and I will test if the modified plants will be a suitable genetic material for the generation of new stable epigenetic traits. With the use of genome wide genomics approaches, I will be able to quantify and compare the IBM1 contribution to phenotypes induced by epigenetic alteration in wheat. As wheat is a model crop for monocots and target of intensive breeding, the achievement of this project will allow both to extend IBM1 epigenetic function into monocots, and to test directly its epigenetic complementation as method to facilitate the introduction of epigenetic variation into crops. Wheat is the most extensive cultivated crop worldwide and a target of intense breeding programs, it is used as critical food resource for more than 2.5 billion people, and it is strategically important for the UK economy. Therefore, the genetic material produced in this project will have direct relevance to breeders, allowing the investigation and screening of epigenetic traits relevant to the generation of new wheat varieties. In short, with the proposed project I want to characterize IBM1's role in the epigenetic stability of plant phenotypes, and to develop a strategy to increase fitness of plants with induced epigenetic variation. Following the achievement of the project objectives, it will become possible to generate epigenetic variability without affecting plant development, strongly facilitating the use of epigenetic traits in crop breeding programs.

表观遗传学研究不依赖于DNA序列变化的生物学性状。在植物中，许多这些表观遗传变化是稳定的，并且非常有效地从亲本传递给后代。因此，表观遗传变异是生物变异的重要来源，包括可能改善作物和发展可持续农业的性状。然而，在农业中使用表观遗传性状的主要限制是我们无法在不干扰关键发育途径的情况下诱导植物足够的表观遗传多样性。我的工作假设是，这些对植物发育的表观遗传负面影响可能与一个名为IBM1的基因的表观遗传改变有关。在模式植物拟南芥中，如果IBM1序列在其中一个内含子的关键区域失去DNA甲基化（一个强表观遗传标记），则会产生更短的无功能转录物。由于IBM1的功能对于维持许多基因的正确表观遗传调控至关重要，因此IBM1功能的缺乏会导致表观遗传缺陷的积累，并降低植物的代间适应性。在基因组序列相同但DNA甲基化程度不同的稳定拟南芥植物品系中，我观察到IBM1基因总是以其甲基化版本遗传，这表明该位点DNA甲基化的去除对植物适应性有负面影响。为了验证这一假设，我将研究IBM1基因的不同表观遗传调控与植物表观遗传稳定性、适应性降低之间的关系。我还将测试人工产生对DNA甲基化不敏感的IBM1等位基因是否是一种合适的方法，以避免与表观遗传变异性产生相关的负面影响。显然，在不影响植物适应性的情况下，在植物中产生新的表观遗传变异的可能性，如果直接在作物中进行探索，将产生更大的影响，在那里，新的性状可以用于育种计划。在这个方向上，我的初步研究表明，IBM1的表观遗传调控在小麦中是保守的。因此，在这个项目中，我还将用一个对表观遗传调控不敏感的IBM1等位基因改造小麦，并测试改造后的植物是否适合作为产生新的稳定表观遗传性状的遗传物质。使用全基因组基因组学方法，我将能够量化和比较IBM1对小麦表观遗传改变诱导的表型的贡献。由于小麦是单子房的模式作物和集约育种的目标，本项目的实现将使IBM1的表观遗传功能扩展到单子房，并直接测试其表观遗传互补，作为促进表观遗传变异引入作物的方法。小麦是世界上种植最广泛的作物，也是密集育种计划的目标，它是超过25亿人的重要食物资源，对英国经济具有重要的战略意义。因此，本项目产生的遗传物质将与育种者直接相关，允许研究和筛选与新小麦品种产生相关的表观遗传性状。简而言之，在这个项目中，我想要描述IBM1在植物表型表观遗传稳定性中的作用，并制定一种策略，以增加诱导表观遗传变异的植物适应性。随着项目目标的实现，在不影响植物发育的情况下产生表观遗传变异将成为可能，这将极大地促进表观遗传性状在作物育种计划中的应用。

项目成果

Extrachromosomal circular DNA and structural variants highlight genome instability in Arabidopsis epigenetic mutants.

• DOI: 10.1038/s41467-023-41023-0
• 发表时间: 2023-08-28
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Zhang, Panpan;Mbodj, Assane;Soundiramourtty, Abirami;Llauro, Christel;Ghesquiere, Alain;Ingouff, Mathieu;Slotkin, R. Keith;Pontvianne, Frederic;Catoni, Marco;Mirouze, Marie
• 通讯作者: Mirouze, Marie