Function and Mechanisms of Epigenetic Stability and Dynamics in Arabidopsis

拟南芥表观遗传稳定性和动态的功能和机制

• 批准号: 10406642
• 负责人: Mary Gehring
• 金额: $ 48.75万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406642
• 关键词: Aberrant DNA Methylation; Address; Arabidopsis; Area; Biological Models; Cells; Code; DNA; DNA Methylation; DNA Modification Methylases; DNA Transposable Elements; DNA glycosylase; Development; Disease; Epigenetic Process; Eukaryota; Female; Fertilization; Gene Expression; Gene Silencing; Generations; Genes; Genetic; Genetic Models; Genetic Transcription; Genome; Genomic Imprinting; Genomics; Germ Cells; Growth and Development function; Heritability; Homeostasis; Laboratories; Malignant Neoplasms; Methylation; Modification; Mouse-ear Cress; Pathway interactions; Placenta; Process; Proteins; Regulation; Repression; Reproduction; Research; Seeds; System; Time; Tissues; comparative; cost; demethylation; epigenome; imprint; methylation pattern; neuronal cell body; prevent; reproductive development; response

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.

项目概要/摘要 我的研究重点是定义表观遗传修饰。 发育过程中表观基因组动态的范围、机制和功能后果， 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、转座元件 (TE) 抑制和调节 DNA 甲基化集中在 TE 中以阻止其转录和转录。 增殖，但这种基因组防御系统有一个潜在的代价——基因组的甲基化 TE 或其残余物可能会不适当地沉默近端蛋白质编码的转录 5-甲基胞嘧啶 DNA 糖基化酶（也称为 DNA 去甲基酶）如何发挥抵消 DNA 甲基转移酶的作用。 拮抗活动得到平衡，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 甲基化并可以表达——是真核生物的一个主要问题，也是研究的焦点之一 我们目前在这一领域的研究将显着增进对如何实现这一目标的理解。 表观遗传途径的活性根据表观基因组的状态进行调节，以及如何调节 这些信息在细胞、发育和世代时间尺度上进行整合。 尽管表观遗传稳态似乎是体细胞的主要力量，但从发育角度来看 受调控的表观遗传重编程对于 DNA 的成功繁殖至关重要。 雌配子中的去甲基化在胎盘样细胞中建立了印记基因表达 受精后胚外种子组织的一个关键的未解答的问题是表观遗传。 DNA 去甲基化引发的变化随后是否维持，当 受精后，当细胞呈现出不同的特征时，母本和父本基因组会结合在一起 我的实验室应用多种遗传、基因组、计算和比较方法。 解决表观遗传学中这些基本问题的进化方法。