Chromatin of repetitive elements

重复元件的染色质

• 批准号: 10374159
• 负责人: Mario Halic
• 金额: $ 35.9万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10374159
• 关键词: Address; Binding Proteins; Biochemistry; Biogenesis; Biological Process; Biology; Cell Nucleolus; Cells; Characteristics; Chromatin; Chromatin Structure; Cryoelectron Microscopy; DNA Sequence; DNA Transposable Elements; DNA-Binding Proteins; Data; Defect; Elements; Environment; Eukaryotic Cell; Event; Evolution; Fission Yeast; Genes; Genetic; Genetic Transcription; Genome; Genome Stability; Genomics; Goals; Heterochromatin; Human; Invaded; Knowledge; Lead; Liquid substance; Location; Malignant Neoplasms; Mediating; Molecular Biology; Mutate; Mutation; Nucleosomes; Parasites; Pathway interactions; Phase; Play; Positioning Attribute; Proteins; RNA; RNA Interference; Regulation; Repetitive Sequence; Research; Ribosomal DNA; Ribosomal RNA; Ribosomes; Role; Site; Sorting - Cell Movement; Sterility; Structure; System; Tandem Repeat Sequences; Time; Transcriptional Silencer Elements; Work; Yeasts; base; cancer cell; cancer genome; cell growth; chromatin protein; fibrillarin; fighting; genetic element; genetic information; genome integrity; in vivo; next generation; nucleophosmin; particle; physical separation; prevent

Summary Silencing of transposable and repetitive elements maintains genome integrity, and defects in silencing pathways lead to cancer formation. Despite the importance, little is known how transposable and repetitive elements are initially recognized and targeted for silencing and how they regulate important biological processes. To address this knowledge gap, we will combine genetics and molecular biology with biochemistry and cryo-EM. Genomes are under constant threat of invasion by transposable elements and other genomic parasites. These foreign genomic elements will use the host for their own expression and proliferation. Silencing of existing transposable and repetitive elements has been well studied, however, little is known how new transposable elements are recognized. Although most of the repetitive genome consist of transposable and other foreign elements, repeats of ribosomal DNA (rDNA) form a unique type of a repetitive genome, in which some repeats are silenced while others are highly expressed. rDNA is localized in the nucleolus, a special compartment that is considered to be phase separated by nucleophosmin and fibrillarin, and where ribosome assembly occurs. Despite the importance of the rDNA locus, it is largely unknown how chromatin structure at rDNA is regulated. The major goals of the proposed research is to determine how new transposable elements are recognized and how and why chromatin regulates sorting and separation of nascent ribosomes. Guided by the strong preliminary data, we propose to pursue two Specific Aims to understand biology of repetitive elements. We will determine what features in invasion of new transposable elements are recognized by the host and which host machineries can discover those elements (Aim 1). Moreover, we will combine cryo-EM with biochemistry and genetics to determine the role of chromatin in ribosome biogenesis (Aim 2). Together, our proposed studies will have broad impact in chromatin field by showing how chromatin regulates ribosome biogenesis and how insertions of new transposons are recognized by the host. Our long-term goals are to understand the regulation of genome expression by chromatin and discover why mutations in chromatin proteins lead to the formation of cancer cells.

概括 转座和重复元件的沉默可维持基因组完整性和沉默缺陷 途径导致癌症形成。尽管很重要，但人们对转置和重复性的了解却很少。 元素最初被识别并针对沉默以及它们如何调节重要的生物 流程。为了弥补这一知识差距，我们将把遗传学和分子生物学与 生物化学和冷冻电镜。 基因组不断受到转座元件和其他基因组寄生虫入侵的威胁。 这些外源基因组元件将利用宿主进行自身的表达和增殖。沉默 现有的转座和重复元件已得到充分研究，但是，很少有人知道新的元件是如何产生的。 转座因子被识别。尽管大多数重复基因组由转座基因和 与其他外来元素相比，核糖体 DNA (rDNA) 的重复形成了重复基因组的独特类型， 其中一些重复被沉默，而另一些则被高度表达。 rDNA 定位于核仁， 被认为是由核磷蛋白和纤维蛋白相分离的特殊隔室，并且其中 发生核糖体组装。尽管 rDNA 位点很重要，但染色质如何作用仍知之甚少。 rDNA 的结构受到调节。拟议研究的主要目标是确定新的 转座元件的识别以及染色质如何以及为何调节转座元件的排序和分离 新生核糖体。 在强有力的初步数据的指导下，我们建议追求两个具体目标来了解 重复的元素。我们将确定新转座因子入侵的特征是什么 被主机识别以及哪些主机可以发现这些元素（目标 1）。此外，我们将冷冻电镜与生物化学和遗传学相结合，以确定 核糖体生物合成中的染色质（目标 2）。 总之，我们提出的研究将通过展示染色质如何在染色质领域产生广泛的影响 调节核糖体生物合成以及宿主如何识别新转座子的插入。我们的 长期目标是了解染色质对基因组表达的调节并找出原因 染色质蛋白的突变导致癌细胞的形成。