Molecular mechanisms of interplay between ethylene signaling and chromatin regulation in Arabidopsis

拟南芥乙烯信号传导与染色质调控相互作用的分子机制

• 批准号: 9113045
• 负责人: Hong Qiao
• 金额: $ 29.75万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9113045
• 关键词: Acetyltransferase; Alleles; Animals; Arabidopsis; Asthma; Binding; Biochemical; Biological Assay; C-terminal; Cell Nucleus; Cells; Cellular biology; Chromatin; Cleaved cell; Communication; Cues; DNA Sequence; Data; Development; Diabetes Mellitus; Disease; Droughts; Endoplasmic Reticulum; Environment; Enzymes; Ethylenes; Eukaryota; Event; Exhibits; Floods; Fruit; Functional disorder; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genome; Genomic approach; Germination; Goals; Health; Heart Hypertrophy; Hereditary Disease; Histone Acetylation; Histones; Homeostasis; Hormones; Immunoprecipitation; Infection; Investigation; Knowledge; Lead; Life Cycle Stages; Link; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Membrane; Modeling; Modification; Molecular; Neurodegenerative Disorders; Nuclear; Nuclear Translocation; Organism; Pathogenesis; Pharmaceutical Preparations; Plant Leaves; Plants; Play; Process; Proteins; Recruitment Activity; Regulation; Research; Role; Seeds; Signal Pathway; Signal Transduction; Stress; System; Techniques; Transcriptional Regulation; Work; Yeasts; base; cancer genetics; chromatin remodeling; functional genomics; genetic manipulation; histone modification; human disease; mutant; novel; novel strategies; plant growth/development; response; screening; senescence; transcription factor; transmission process; tumor progression; yeast two hybrid system

 DESCRIPTION (provided by applicant): The function of the nucleus is to maintain the integrity of genes and to control the activities of the cell by regulating gene expression. Nuclear enzymes, chromatin and its modifications contribute to the abilities of cells and organisms to respond and survive in dynamic environments. Dysfunctions nuclear processes contribute directly to cancer progression and genetic disorders. We are using Arabidopsis to study early nuclear events in ethylene signaling, which is important not only in plant growth and development, but also in various responses to stresses such as drought, flooding, and infection. Our long-term goal is to develop a validated mechanistic model that accurately describes how chromatin regulators receive signals and how the regulation is established in the first place in ethylene signaling. In the ethylene signaling pathway, EIN2 is the essential key regulator, and it is the only gene whose null mutant renders completely ethylene insensitive. Our recent studies have revealed that EIN2 mediates transmission of ethylene signaling that originates at the endoplasmic reticulum membrane to the nucleus and that the EIN2 C-terminus is cleaved and translocated to the nucleus to initiate the ethylene response. However, the molecular mechanism that nuclear translocation of EIN2, the function of EIN2 C-terminal end in the nucleus and how EIN2 C-terminal end communicate with EIN3 are not understood. Through extensive yeast two-hybrid screening and immunoprecipitation followed by mass spectrometry assay, we identified a strong EIN2 C-terminus interactor. This protein is localized to the nucleus, and strikingly, it is associated with histones and involved in the regulation of histone modifications. Our preliminary data strongly indicate that the EIN2 C-terminus participates in histone modification, providing a link between signaling and chromatin regulation. This proposal has the following specific aims: (1) Determine the function of EIN2 C-terminus and identify and characterize functions of other components involved in the early nuclear response to ethylene signaling; (2) Uncover the mechanism that how chromatin regulators receive ethylene signaling to regulate the initiation of the specific transcriptional regulation. The molecular mechanisms under investigation involve chromatin regulation and transcriptional reprogramming, which are shared in general in both plants and animals; (3) Elucidate the molecular mechanisms by which EIN2 C-terminal is translocated to the nucleus in response to ethylene.

 描述（由适用提供）：核心的功能是维持基因的完整性，并通过控制基因表达来控制细胞的活性。核酶，染色质及其修饰有助于细胞和组织在动态环境中做出反应和生存的能力。功能障碍核过程直接导致癌症进展和遗传疾病。我们正在使用拟南芥来研究乙烯信号传导中的早期核事件，这不仅在植物生长和发育中很重要，而且对干旱，洪水和感染等压力的各种反应也很重要。我们的长期目标是开发一个经过验证的机械模型，该模型准确地描述了染色质调节器如何接收信号以及如何在乙烯信号中建立调节。在乙烯信号通路中，EIN2是必不可少的关键调节剂，它是唯一的基因，其无效突变体使乙烯完全不敏感。我们最近的研究表明，EIN2介导了乙烯信号的传播，该信号的传播起源于内质网膜到核，并将EIN2 C末端切割并翻译成核以启动乙烯反应。但是，EIN2的核转运，核中EIN2 C末端的功能以及EIN2 C末端如何与EIN3通信的分子机制。通过广泛的酵母两杂化筛查和免疫沉淀，然后进行质谱测定法，我们确定了强大的EIN2 C末端相互作用。该蛋白质位于细胞核， 令人惊讶的是，它与组蛋白有关，并参与组蛋白修饰的调节。我们的初步数据强烈表明EIN2 C末端参与组蛋白的修饰，提供信号传导和染色质调节之间的联系。该建议具有以下特定目的：（1）确定EIN2 C末端的功能，并确定和表征与乙烯信号早期核反应有关的其他组件的功能； （2）发现染色质调节剂如何接收乙烯信号传导以调节特定转录调控的倡议的机制。所研究的分子机制涉及染色质调节和转录重编程，这些调节在动植物中通常共享。 （3）阐明EIN2 C末端以响应乙烯易位的分子机制。