Function and Mechanisms of Epigenetic Stability and Dynamics in Arabidopsis

项目概要/摘要 表观遗传修饰调节基因组功能。我的研究重点是定义 范围、机制和发育过程中表观基因组动态的功能后果， 使用强大的遗传模型系统拟南芥。DNA甲基化（5- 甲基胞嘧啶）是一种与高度交织的过程相关的可遗传的表观遗传标记 包括转录基因沉默、转座因子（TE）抑制和 基因组印记DNA甲基化集中在TE中以防止其转录， 增殖，但这种基因组防御系统是有潜在代价的-甲基化 TE或其残余物可以不适当地沉默近端蛋白编码的转录， 基因.通过5-甲基胞嘧啶DNA糖基化酶（也称为甲基化酶）的活性DNA去甲基化 DNA脱甲基酶）起抵消DNA甲基转移酶的作用。但这两个人 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， 转座因子保持甲基化和沉默，基因保持相对自由， 甲基化并可以表达-是真核生物中的一个主要问题，也是研究的焦点之一。 我们目前的研究。我们在这一领域的努力将大大增加人们对 表观遗传途径的活性响应于表观基因组的状态而被调节， 这些信息在细胞、发育和世代时间尺度上被整合。 虽然表观遗传的稳态似乎是索马的主要力量，但在发育上- 受调控的表观遗传重编程对成功繁殖至关重要。DNA 雌性配子中的去甲基化在胎盘样细胞中建立印记基因表达 受精后的胚外种子组织。一个关键的未解问题是表观遗传 由DNA去甲基化引发的变化随后被维持，或不被维持，当 在受精后，随着细胞呈现出不同的 身份我的实验室应用了不同的遗传学，基因组学，计算和比较 进化方法来解决表观遗传学中的这些基本问题。

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.