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

基本信息

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
项目类别：
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

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

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项目摘要

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）是与高度交织过程相关的可遗传表观遗传标记包括转录基因沉默，转座元件（TE）表达和调节基因组印记。 DNA甲基化集中在TES中，以防止其转录和扩散，但这种基因组防御系统的潜在成本 - 甲基化 TE或它们的残余物可能不适当地使近端蛋白质编码的转录保持沉默基因。通过5-甲基胞嘧啶DNA糖基酶进行活性DNA脱甲基（也称为 DNA去甲基酶的功能可抵消DNA甲基转移酶。但是这两个如何拮抗活性是平衡的，可以将基因组保持在稳定的表观遗传状态 - 转座元素保持甲基化并保持沉默，并保持基因相对较不受欢迎甲基化并可以表达 - 是真核生物之间的一个主要问题，是我们目前的研究。我们在这一领域的努力将大大增加对表观遗传途径的活性是根据表观遗传组的状态调节的该信息是在细胞，发育和世代的时间尺度上集成的。尽管表观遗传稳态似乎是躯体中的主要力量，但在开发中 - 受调节的表观遗传重编程对于成功繁殖至关重要。脱氧核糖核酸女配子中的脱甲基化建立了斑点样的烙印基因表达受精后胚胎外种子组织。一个关键的未解决的问题是表观遗传学随后，当DNA脱甲基引发的变化随后被维持，无论是否在施肥后将母体和prot骨基因组组合在一起，并且随着细胞的不同身份。我的实验室应用多种遗传，基因组，计算和比较进化方法是在表观遗传学中解决这些基本问题。