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.

项目摘要 核酶，染色质及其修饰介导细胞和生物对 动态环境。染色质重塑通过提供转录来影响基因表达 因素和转录机械，具有动态访问原本包装的基因组。 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。但是，关于新陈代谢的了解知之甚少 状态和染色质调节是协调的，以允许细胞和生物对环境做出反应 状况。我们正在使用拟南芥研究乙烯中的代谢状态和染色质调节 信号。我们的小组率先研究了乙烯信号传导中组蛋白调节的研究。乙烯信号是 在内质网（ER）膜上感知到EIN2的裂解和核易位 将信号从ER膜介导到核。 EIN2 C末端（EIN2-C）被裂解，并且 转移到核以启动乙烯反应。在最后一个资金期间，我们 发现EIN2是一个必不可少的信号因子，也是组蛋白的关键组成部分 直接调节H3K14AC和H3K23AC以介导转录响应的修改 到乙烯。因此，EIN2是乙烯信号传导和染色质调节之间的直接联系。我们 还鉴定了一个非官方组蛋白乙酰转移酶（HAT）含有域的蛋白质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链接 EIN2介导的乙烯信号传导，用EIN2杀手的组蛋白乙酰化调节。令人惊讶的是，我们的新人 数据提供了可靠的证据，表明丙酮酸脱氢酶复合物转化了丙酮酸 与组蛋白乙酰化的乙酰基乙酰辅酶A乙酰辅酶A与Ein2-C相互作用，并且亚基 该复合物的响应响应于乙烯，可以从线粒体转移到核。这 新发现为乙酰基-COA生物合成涉及的假设提供了强烈的理性。 EIN2介导的染色质调节和乙烯信号传导之间的相互作用。在此提案中，我们将 通过关注以下特定 目的：（1）阐明响应EIN2依赖性组蛋白修饰的详细机制 到乙烯； （2）研究丙酮酸代谢酶在EIN2-中的功能 响应乙烯的介导染色质和转录调节，（3）阐明分子 EIN2-C响应乙烯的机制易位到核。我们的工作将 由于核过程功能障碍直接导致癌症进展和 新陈代谢和染色质活性之间的遗传疾病和失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