Investigate the molecular mechanisms of the interplay between cell metabolism and histone modification in ethylene signaling in Arabadopsis

研究拟南芥乙烯信号传导中细胞代谢与组蛋白修饰相互作用的分子机制

• 批准号: 10669621
• 负责人: Hong Qiao
• 金额: $ 33.5万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10669621
• 关键词: Acetyl Coenzyme A; Anabolism; Arabidopsis; Binding; Biochemical; Cell Nucleus; Cells; Cellular Metabolic Process; Chromatin; Chromatin Structure; Complex; Cues; DNA Sequence; Data; Disease; Endoplasmic Reticulum; Environment; Enzymes; Epigenetic Process; Ethylenes; Eukaryota; Fruit; Functional disorder; Funding; Gene Expression; Gene Expression Regulation; Genetic; Genetic Diseases; Genetic Transcription; Genome; Genomic approach; Germination; Goals; Histone Acetylation; Histones; Hormones; Life Cycle Stages; Link; Mediating; Membrane; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolism; Mitochondria; Modeling; Modification; Molecular; Nuclear; Nuclear Translocation; Organism; Phenotype; Plant Leaves; Plants; Play; Process; Protein Dephosphorylation; Proteins; Pyruvate; Pyruvate Dehydrogenase Complex; Regulation; Role; Seedling; Signal Transduction; Solid; Transcriptional Regulation; Work; cancer genetics; chromatin remodeling; cofactor; functional genomics; histone acetyltransferase; histone modification; histone-binding proteins; hormonal signals; metabolic abnormality assessment; pyruvate dehydrogenase; recruit; response; senescence; transcription factor; tumor progression

Project Summary Nuclear enzymes, chromatin and its modifications mediate the responses of cells and organisms to dynamic environments. Chromatin remodeling influences gene expression by providing transcription factors and the transcription machinery with dynamic access to an otherwise tightly packaged genome. Many chromatin-modifying enzymes require metabolites as cofactors; therefore, the cell metabolic state can influence chromatin structure and epigenetic processes. However, little is known about how metabolic states and chromatin regulation are coordinated to allow cells and organisms to respond to environmental conditions. We are using Arabidopsis to study the metabolic states and chromatin regulation in ethylene signaling. Our group pioneered the study of histone regulation in ethylene signaling. The ethylene signal is perceived on the endoplasmic reticulum (ER) membrane, and the cleavage and nuclear translocation of EIN2 mediates the signal from the ER membrane to the nucleus. The EIN2 C-terminus (EIN2-C) is cleaved and translocated to the nucleus to initiate the ethylene response. During the last funding period, we discovered that EIN2, an essential signaling factor, is also a key component of the histone modification that directly regulates H3K14Ac and H3K23Ac to mediate the transcriptional response to ethylene. EIN2 is thus the direct link between ethylene signaling and chromatin regulation. We also identified a noncanonical histone acetyltransferase (HAT) domain-containing protein EHAT that directly interacts with the EIN2-C in the nucleus. Our preliminary data strongly suggest that EHAT links EIN2-mediated ethylene signaling with EIN2-meidated regulation of histone acetylation. Strikingly, our new data provide solid evidence that the pyruvate dehydrogenase complex, which converts pyruvate to acetyl-CoA, the acetyl-donor of histone acetylation, interacts with EIN2-C and that the subunits of the complex can translocate from the mitochondria to the nucleus in response to ethylene. This new discovery provides a strong rational for the hypothesis that acetyl-CoA biosynthesis is involved in the EIN2-mediated interplay between chromatin regulation and ethylene signaling. In this proposal, we will study metabolic states and chromatin regulation in ethylene signaling by focusing on the following specific aims: (1) elucidate the detailed mechanisms governing EIN2-dependent histone modification in response to ethylene; (2) investigate the function of the metabolic enzyme pyruvate dehydrogenase in EIN2- mediated chromatin and transcriptional regulation in response to ethylene, and (3) elucidate the molecular mechanisms by which the EIN2-C is translocated to the nucleus in response to ethylene. Our work will have broad implications as dysfunctions of nuclear processes contribute directly to cancer progression and genetic disorders and imbalances between metabolism and chromatin activities can trigger severe metabolic disease.

项目概要 核酶、染色质及其修饰介导细胞和生物体对 动态环境。染色质重塑通过提供转录影响基因表达 因子和转录机制可以动态访问紧密包装的基因组。 许多染色质修饰酶需要代谢物作为辅助因子；因此，细胞代谢状态 可以影响染色质结构和表观遗传过程。然而，人们对于新陈代谢如何进行知之甚少。 状态和染色质调节相互协调，使细胞和生物体能够对环境做出反应 状况。我们正在利用拟南芥来研究乙烯的代谢状态和染色质调控 发信号。我们小组率先研究了乙烯信号传导中的组蛋白调控。乙烯信号为 内质网 (ER) 膜上的感知，以及 EIN2 的裂解和核转位 介导从内质网膜到细胞核的信号。 EIN2 C 末端 (EIN2-C) 被切割并 易位至细胞核以引发乙烯反应。在上一个资助期间，我们 发现EIN2是一种重要的信号传导因子，也是组蛋白的关键组成部分 直接调节 H3K14Ac 和 H3K23Ac 介导转录反应的修饰 至乙烯。因此，EIN2 是乙烯信号传导和染色质调控之间的直接联系。我们 还鉴定出一种包含非经典组蛋白乙酰转移酶 (HAT) 结构域的蛋白质 EHAT， 直接与细胞核中的 EIN2-C 相互作用。我们的初步数据强烈表明 EHAT 与 EIN2 介导的乙烯信号传导与 EIN2 介导的组蛋白乙酰化调节。引人注目的是，我们的新 数据提供了确凿的证据，证明丙酮酸脱氢酶复合物可将丙酮酸转化为丙酮酸。 乙酰辅酶A（组蛋白乙酰化的乙酰基供体）与EIN2-C相互作用，并且亚基 该复合物的一部分可以响应乙烯而从线粒体转移到细胞核。这 新发现为乙酰辅酶A生物合成参与这一假设提供了强有力的理由 EIN2 介导的染色质调节和乙烯信号传导之间的相互作用。在本提案中，我们将 通过关注以下具体内容来研究乙烯信号传导中的代谢状态和染色质调控 目的：(1) 阐明控制 EIN2 依赖性组蛋白修饰响应的详细机制 乙烯； (2)考察EIN2-中代谢酶丙酮酸脱氢酶的功能 介导的染色质和转录调控响应乙烯，以及（3）阐明分子 EIN2-C 响应乙烯而易位至细胞核的机制。我们的工作将 具有广泛的影响，因为核过程的功能障碍直接导致癌症进展和 遗传性疾病以及代谢和染色质活性之间的不平衡会引发严重的代谢 疾病。

项目成果

ENAP1 retrains seed germination via H3K9 acetylation mediated positive feedback regulation of ABI5.

• DOI: 10.1371/journal.pgen.1009955
• 发表时间: 2021-12
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Zhao B;Wang L;Shao Z;Chin K;Chakravarty D;Qiao H
• 通讯作者: Qiao H

Abscisic acid negatively regulates the Polycomb-mediated H3K27me3 through the PHD-finger protein, VIL1.

• DOI: 10.1111/nph.18156
• 发表时间: 2022-08
• 期刊: NEW PHYTOLOGIST
• 影响因子: 9.4
• 作者: Zong, Wei;Kim, Junghyun;Bordiya, Yogendra;Qiao, Hong;Sung, Sibum
• 通讯作者: Sung, Sibum

MYB44-ENAP1/2 restricts HDT4 to regulate drought tolerance in Arabidopsis.

• DOI: 10.1371/journal.pgen.1010473
• 发表时间: 2022-11
• 期刊: PLoS genetics
• 影响因子: 4.5

Phosphorylation status of Bβ subunit acts as a switch to regulate the function of phosphatase PP2A in ethylene-mediated root growth inhibition.

• DOI: 10.1111/nph.18467
• 发表时间: 2022-12
• 期刊: NEW PHYTOLOGIST
• 影响因子: 9.4
• 作者: Shao, Zhengyao;Zhao, Bo;Kotla, Prashanth;Burns, Jackson G.;Tran, Jaclyn;Ke, Meiyu;Chen, Xu;Browning, Karen S.;Qiao, Hong
• 通讯作者: Qiao, Hong

TREE1-EIN3-mediated transcriptional repression inhibits shoot growth in response to ethylene.

• DOI: 10.1073/pnas.2018735117
• 发表时间: 2020-11-17
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Wang L;Ko EE;Tran J;Qiao H
• 通讯作者: Qiao H