Function and Mechanisms of Epigenetic Stability and Dynamics in Arabidopsis

项目摘要/摘要 表观遗传修饰调节基因组功能。我的研究重点是定义 表观基因组动力学在发育过程中的范围、机制和功能后果， 利用功能强大的遗传模型系统拟南芥。DNA甲基化(5- 甲基胞嘧啶)是一种可遗传的表观遗传标记，与高度相互交织的过程有关 包括转录基因沉默、转座元件(TE)抑制和调节 基因组印记。DNA甲基化集中在TES中，以防止其转录和 但这种基因组防御系统是有潜在代价的--甲基化 TES或其残基可不适当地沉默近端蛋白编码的转录 基因。5-甲基胞嘧啶DNA糖基酶(也称为 DNA去甲基酶)起到对抗DNA甲基转移酶的作用。但这两个人怎么 拮抗活性是平衡的，以维持基因组处于稳定的表观遗传状态-其中 转座元件保持甲基化和沉默，基因保持相对自由 甲基化和可表达-是真核生物中的一个主要问题，也是 我们目前的研究。我们在这方面的努力将大大增加人们对 表观遗传途径的活性是根据表观基因组的状态以及如何进行调节的 这些信息是在细胞、发育和世代的时间尺度上整合的。 虽然表观遗传动态平衡似乎是体细胞的主要力量，但在发育上- 受调控的表观遗传重编程是成功繁殖的关键。脱氧核糖核酸 雌配子去甲基化在胎盘样中建立印记基因表达 受精后的胚外种子组织。一个关键的悬而未决的问题是表观遗传学 在以下情况下，由DNA去甲基化引发的变化随后会保持不变 母亲和父亲的基因组在受精后结合在一起，AS细胞呈现出不同的 身份。我的实验室应用了不同的遗传、基因组、计算和比较 在表观遗传学中解决这些基本问题的进化方法。

Project Summary/Abstract Epigenetic modifications regulate genome function. My research is focused on defining the scope, mechanisms, and functional consequences of epigenome dynamics during development, using the powerful genetic model system Arabidopsis thaliana. DNA methylation (5- methylcytosine) is a heritable epigenetic mark associated with highly intertwined processes including transcriptional gene silencing, transposable element (TE) repression, and regulation of genomic imprinting. DNA methylation is concentrated in TEs to prevent their transcription and proliferation, but this genome defense system comes at a potential cost – the methylation of TEs or their remnants can inappropriately silence the transcription of proximal protein-coding genes. Active DNA demethylation by 5-methylcytosine DNA glycosylases (also referred to as DNA demethylases) functions to counteract DNA methyltransferases. But how these two antagonistic activities are balanced to maintain the genome in a stable epigenetic state – where transposable elements are kept methylated and silenced and genes are kept relatively free of methylation and can be expressed – is a major question across eukaryotes and is one focus of our current research. Our efforts in this area will significantly increase understanding of how the activity of epigenetic pathways is modulated in response to the state of the epigenome and how this information is integrated over cellular, developmental, and generational time scales. Although epigenetic homeostasis appears to be a major force in the soma, developmentally- regulated epigenetic reprogramming is essential for successful reproduction. DNA demethylation in the female gamete establishes imprinted gene expression in a placenta-like extra-embryonic seed tissue after fertilization. A critical unanswered question is how epigenetic changes that are initiated by DNA demethylation are subsequently maintained, or not, when maternal and paternal genomes are combined after fertilization and as cells take on distinct identities. My laboratory applies diverse genetic, genomic, computational, and comparative evolutionary approaches to address these fundamental questions in epigenetics.