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: 9262954
• 负责人: Hong Qiao
• 金额: $ 29.84万
• 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/9262954
• 关键词: 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; Heart Hypertrophy; Hereditary Disease; Histone Acetylation; Histone Deacetylase; Histones; Homeostasis; Hormones; Immunoprecipitation; Infection; Investigation; Knowledge; Life Cycle Stages; Link; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Membrane; Modeling; Modification; Molecular; Neurodegenerative Disorders; Nuclear; Nuclear Translocation; Organism; Pathogenesis; Pharmaceutical Preparations; Phenotype; Plant Leaves; Plants; Play; Process; Proteins; Recruitment Activity; Regulation; Research; Role; Seeds; Signal Pathway; Signal Transduction; Stress; System; Techniques; Transcription Initiation; Transcriptional Regulation; Work; Yeasts; cancer genetics; chromatin remodeling; functional genomics; genetic manipulation; histone acetyltransferase; histone modification; human disease; mutant; novel; novel strategies; plant growth/development; public health relevance; 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(申请人提供)：核的功能是维持基因的完整性，并通过调节基因表达来控制细胞的活动。核酶、染色质及其修饰有助于细胞和生物体在动态环境中响应和生存的能力。核过程功能障碍直接导致癌症进展和遗传性疾病。我们正在利用拟南芥来研究乙烯信号的早期核事件，这不仅在植物的生长和发育中很重要，而且在对干旱、洪水和感染等逆境的各种反应中也是重要的。我们的长期目标是开发一个经过验证的机制模型，准确描述染色质调节器如何接收信号，以及调控是如何首先在乙烯信号中建立的。在乙烯信号转导途径中，EIN2是必需的关键调节因子，也是唯一一个其零突变使乙烯完全不敏感的基因。我们最近的研究表明，EIN2介导了起源于内质网膜的乙烯信号向细胞核的传递，并且EIN2的C末端被裂解并移位到细胞核以启动乙烯反应。然而，EIN2的核转位的分子机制、EIN2的C末端在细胞核内的功能以及EIN2的C末端如何与EIN3进行通讯等尚不清楚。通过广泛的酵母双杂交筛选和免疫沉淀以及质谱分析，我们鉴定了一个很强的EIN2-末端相互作用元件。这种蛋白质定位于细胞核， 引人注目的是，它与组蛋白相关，并参与组蛋白修饰的调节。我们的初步数据有力地表明，EIN2的C末端参与了组蛋白的修饰，提供了信号和染色质调节之间的联系。该建议有以下具体目的：(1)确定EIN2 C-末端的功能，并鉴定和鉴定参与乙烯信号早期核反应的其他成分的功能；(2)揭示染色质调节因子如何接收乙烯信号以调节特定转录调控的启动机制。正在研究的分子机制包括染色质调节和转录重编程，这在植物和动物中普遍存在；(3)阐明EIN2 C末端移位到细胞核以响应乙烯的分子机制。