Actions of DRM3 on DRM2 mediated DNA methylation

DRM3 对 DRM2 介导的 DNA 甲基化的作用

• 批准号: 8056445
• 负责人: XUEHUA ZHONG
• 金额: $ 5.3万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056445
• 关键词: Address; Animal Model; Animals; Arabidopsis; Baculovirus Expression System; Biological; Biological Assay; Biology; Cancer Etiology; Cardiovascular Diseases; Cardiovascular system; Chemicals; Chromatin; DNA; DNA Methylation; DNA Methyltransferase; DNA Modification Methylases; DNA Sequence; Data; Enhancers; Epigenetic Process; Gene Expression; Gene Targeting; Genetic; Genetic Screening; Genomics; Human; Human Genome; Human body; In Vitro; Investigation; Knowledge; Length; Maintenance; Malignant Neoplasms; Mediating; Methylation; Methyltransferase; Molecular; Mouse-ear Cress; Organism; Orthologous Gene; Pathway interactions; Phenotype; Plants; Process; Proteins; RNA; RNA Interference; Recombinants; Recruitment Activity; Research; Resources; Role; Selfish DNA; Series; System; Testing; base; genome-wide; insight; interest; mutant; paralogous gene; research study; tool; tumorigenesis

DESCRIPTION (provided by applicant): This project seeks to gain groundbreaking insights into an unresolved problem in biology that has vast importance to understand the molecular basis of cardiovascular disease: how specific DNA sequences are targeted for methylation. DNA methylation confers epigenetic control of gene expression in many organisms. Global alterations of DNA methylation are now widely recognized as a contributing factor in human cancer and cardiovascular. Despite the profound biological importance of DNA methylation, how particular DNA sequences are initially targeted for methylation remains largely unknown. We propose to address this question by investigating the mechanism of DRM2-mediated DNA methylation through the investigation of the role of DRM3, a catalytically inactive homology of DRM2, in targeting DRM2 to chromatin (Aim 1) and stimulating DRM2 methyltransferase catalytic activity (Aim 2). I will also identify new components that assist in DRM3 function by genetic screen (Aim 3). Completion of these studies will provide important new information about the molecular factors and interactions that recognize specific DNA sequences to initiate methylation. Because DNA methylation is highly conserved among plants and animals, results from this project are expected to help accelerate studies to understand the mechanisms of tumorigenesis and cardiovascular diseases caused by DNA methylation. PUBLIC HEALTH RELEVANCE: The human genome not only contains the basic genetic information for making a human body, but also contains "selfish DNAs" that function only to replicate themselves and their uncontrolled replication can cause cancers. The human body has a defense system to recognize and then add a special chemical mark, called methylation, on these DNAs to stop their replication. This project seeks to understand the molecular basis of how specific DNA sequences are recognized and targeted for methylation.

描述（由申请人提供）：该项目旨在对生物学中尚未解决的问题获得突破性的见解，该问题对于理解心血管疾病的分子基础非常重要：特定的 DNA 序列如何靶向甲基化。 DNA 甲基化赋予许多生物体基因表达的表观遗传控制。 DNA 甲基化的整体改变现在被广泛认为是人类癌症和心血管疾病的一个促成因素。尽管 DNA 甲基化具有深远的生物学重要性，但特定的 DNA 序列最初如何被定位为甲基化仍然很大程度上未知。我们建议通过研究DRM3（DRM2的催化失活同源物）在将DRM2靶向染色质（目标1）和刺激DRM2甲基转移酶催化活性（目标2）中的作用来研究DRM2介导的DNA甲基化机制来解决这个问题。 ）。我还将通过基因筛选来鉴定有助于 DRM3 功能的新成分（目标 3）。这些研究的完成将提供有关识别特定 DNA 序列以启动甲基化的分子因素和相互作用的重要新信息。由于DNA甲基化在植物和动物中高度保守，该项目的结果预计将有助于加速研究，了解DNA甲基化引起的肿瘤发生和心血管疾病的机制。 公共健康相关性：人类基因组不仅包含构成人体的基本遗传信息，还包含仅具有自我复制功能的“自私DNA”，其不受控制的复制可能导致癌症。人体有一个防御系统来识别这些DNA，然后在这些DNA上添加一种特殊的化学标记，称为甲基化，以阻止它们的复制。该项目旨在了解特定 DNA 序列如何被识别和甲基化的分子基础。