Epigenetic regulation of sexual lineage development in plants

植物有性谱系发育的表观遗传调控

• 批准号: BB/L025043/1
• 负责人: Xiaoqi Feng
• 金额: $ 143.15万
• 依托单位: John Innes Centre
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL025043%2F1
• 关键词: Epigenetic; regulation; sexual; lineage; development

A key characteristic of life is the ability to reproduce. Reproductive strategies are major contributors to evolutionary fitness and can vary substantially between species. Like humans, most flowering plants reproduce sexually by mating with another individual; however, unlike humans, plants typically possess both male and female organs, and many plant species, including major crops, are capable of self-fertilization. Sexual reproduction in flowering plants is important to mankind as it produces the seeds that comprise most of our staple food. With decreasing arable land, an exploding population and global climate change, feeding the world in the 21st century will require a step-change in the efficiency of seed production, and this can only come from a deeper understanding of plant reproductive development. Sexual reproduction in plants is carried out by two highly specialized families of cells, here called the male and female sexual lineages (SLs). A fundamental but still unresolved question that has always fascinated me is how SL function and fate are installed and maintained precisely in these cell lineages. My DPhil and postdoctoral studies focused on how genetic and 'epigenetic' pathways contribute to SL function and fertility. 'Epigenetic' regulation - such as DNA methylation - is named after its ability to alter gene expression by modifying the state of DNA without changing its genetic sequence. Recently, I discovered that the RNA-directed DNA methylation (RdDM) pathway regulates SL development in Arabidopsis plants by controlling the expression of several hundred genes. Consistent with the importance of the RdDM pathway in SL development, its mutations cause defects in SL development in both Arabidopsis and maize. My proposed research integrates plant developmental, molecular, genetics and epigenetics biology to investigate how RdDM installs reproductive function and fate in the male SL of the model plant Arabidopsis thaliana. To detect changes in the DNA methylation and gene expression, I have developed state-of-the-art techniques such as fluorescence-activated cell sorting and micromanipulation to isolate all types of male SL cells to high purity. I will use whole-genome sequencing of these SL cells from RdDM mutants to pinpoint the function of the SL-specific RdDM pathway, and a combination of genetics and developmental biology to determine how the genes controlled by the SL-specific RdDM regulate SL development. Finally, through a combination of genomics, developmental biology and mutant screens, I will decipher the mechanism by which RdDM is directed to genes in the SL.This multi-disciplinary program of work will deepen our understanding of male SL development and function by identifying a number of key genetic and epigenetic regulators. Due to the significant parallels between male and female SL development, and because discoveries in the model plant Arabidopsis have been routinely translated into major crops such as rice and maize, these insights will be widely applicable and may be used to improve crop fertility and yield. At a more generic level, my work will demonstrate, for the first time, how epigenetic pathways can be tailored in a specific lineage of cells to convey precise biological functions. This kind of developmental regulation likely affects many biological processes in a wide range of cell types and tissues. I therefore believe that my work will lay a foundation for the study of epigenetic regulation of plant development. Many DNA methylation mechanisms are highly conserved between Arabidopsis and mammals, and recent evidence points to a role for DNA methylation in directing the differentiation of human cell lines. Insights from this work thus have the potential to shed light on the regulation of lineage development by DNA methylation in mammals, which is important to combat DNA methylation-related human diseases such as cancer.

生命的一个关键特征是繁殖能力。繁殖策略是进化适应性的主要贡献者，并且在物种之间可能存在很大差异。与人类一样，大多数开花植物通过与另一个个体交配进行有性繁殖;然而，与人类不同的是，植物通常同时拥有雄性和雌性器官，许多植物物种，包括主要作物，都能够自花受精。开花植物的有性繁殖对人类很重要，因为它产生的种子构成了我们大部分的主食。随着可耕地减少、人口爆炸和全球气候变化，要在世纪养活全世界，种子生产的效率需要逐步提高，而这只能来自对植物生殖发育的更深入理解。植物的有性生殖由两个高度特化的细胞家族进行，这里称为雄性和雌性有性谱系（SL）。一个基本的，但仍然悬而未决的问题，一直吸引着我，是如何SL功能和命运是安装和维护精确地在这些细胞谱系。我的博士和博士后研究集中在遗传和“表观遗传”途径如何有助于SL功能和生育能力。“表观遗传”调控-如DNA甲基化-是因为它能够通过改变DNA的状态而不改变其遗传序列来改变基因表达。最近，我发现RNA指导的DNA甲基化（RdDM）途径通过控制数百个基因的表达来调节拟南芥中SL的发育。与RdDM途径在SL发育中的重要性一致，其突变导致拟南芥和玉米的SL发育缺陷。我建议的研究整合植物发育，分子，遗传学和表观遗传学生物学，研究RdDM如何安装在模式植物拟南芥的雄性SL的生殖功能和命运。为了检测DNA甲基化和基因表达的变化，我开发了最先进的技术，如荧光激活细胞分选和显微操作，以分离所有类型的男性SL细胞到高纯度。我将使用这些SL细胞的全基因组测序从RdDM突变体，以查明SL特异性RdDM途径的功能，并结合遗传学和发育生物学，以确定SL特异性RdDM控制的基因如何调节SL的发展。最后，通过基因组学，发育生物学和突变体筛选相结合，我将破译RdDM是针对SL中的基因的机制。这一多学科的工作计划将加深我们对男性SL的发展和功能的理解，通过确定一些关键的遗传和表观遗传调节。由于雄性和雌性SL发育之间存在显着相似之处，并且由于模式植物拟南芥的发现已被常规转化为水稻和玉米等主要作物，因此这些见解将具有广泛适用性，并可用于提高作物生育力和产量。在更一般的水平上，我的工作将首次展示表观遗传途径如何在特定的细胞谱系中进行定制，以传达精确的生物学功能。这种发育调节可能会影响许多细胞类型和组织中的许多生物过程。因此，我相信我的工作将为植物发育的表观遗传调控研究奠定基础。许多DNA甲基化机制在拟南芥和哺乳动物之间高度保守，最近的证据表明DNA甲基化在指导人类细胞系分化中的作用。因此，这项工作的见解有可能揭示哺乳动物中DNA甲基化对谱系发育的调节，这对于对抗DNA甲基化相关的人类疾病（如癌症）非常重要。

项目成果

DNA methylation dynamics during germline development.

• DOI: 10.1111/jipb.13422
• 发表时间: 2022-12
• 期刊: Journal of integrative plant biology
• 影响因子: 11.4

Natural depletion of H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation

性细胞中 H1 的自然消耗会导致 DNA 去甲基化、异染色质去浓缩和转座子激活

• DOI: 10.1101/451930
• 发表时间: 2018
• 作者: He S

Natural Variation in TBP-ASSOCIATED FACTOR 4b Controls Meiotic Crossover and Germline Transcription in Arabidopsis

• DOI: 10.1016/j.cub.2019.06.084
• 发表时间: 2019-08-19
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Lawrence, Emma J.;Gao, Hongbo;Henderson, Ian R.
• 通讯作者: Henderson, Ian R.

Natural Variation in TBP-ASSOCIATED FACTOR 4b Controls Meiotic Crossover and Germline Transcription in Arabidopsis.

TBP 相关因子 4b 的自然变异控制拟​​南芥减数分裂交叉和种系转录。

• DOI: 10.17863/cam.41357
• 发表时间: 2019
• 作者: Lawrence E