Epigenetic gene regulation in Arabidopsis

拟南芥表观遗传基因调控

• 批准号: 10551231
• 负责人: STEVEN E JACOBSEN
• 金额: $ 31.2万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10551231
• 关键词: Arabidopsis; Binding; Biological Models; Biology; Cancer Etiology; Cells; Chemicals; Cytosine; DNA; DNA Damage; DNA Methylation; DNA Modification Methylases; DNA-Directed RNA Polymerase; Defect; Epigenetic Process; Five-Year Plans; Gene Expression; Gene Expression Regulation; Gene Silencing; Genes; Genetic; Genome; Genome Stability; Genomics; Heterochromatin; Histones; Laboratories; Laboratory Finding; Lead; Maintenance; Mass Spectrum Analysis; Methods; Methylation; Modification; Mouse-ear Cress; Nature; Pathway interactions; Pattern; Play; Post-Translational Protein Processing; Proteins; Proteomics; RNA; Repression; Research; Tissues; Untranslated RNA; derepression; gene function; histone methylation; histone modification; methylation pattern; mutant; prevent; protein complex; response; structural biology

Project Summary/Abstract Our laboratory focuses on the biology and mechanisms of gene silencing by DNA methylation and histone modifications, primarily using Arabidopsis thaliana as a model system. Recent efforts have focused on the mechanisms by which DNA methylation is properly patterned in the genome. The main findings are that four distinct DNA methylation pathways, driven by four different DNA methyltransferases act in self- reinforcing mechanisms to maintain cytosine methylation in three different sequence contexts, CG, CHG and CHH (where H = A, T, or C). The establishment of DNA methylation is controlled by the RNA-directed DNA methylation pathway, and studying this pathway has been a major recent focus of the lab. Most recently, the laboratory has used genetics, genomics, proteomics, and structural biology approaches to characterize the mechanisms by which two RNA polymerases, Pol IV and Pol V, act to produce non- coding RNAs that act to target RNA-directed DNA methylation to specific loci. The newest findings from the laboratory are also taking us into new directions aimed at understanding factors that act downstream of DNA methylation, to both control gene expression and to maintain genome stability. In the next five years, we plan to utilize all available approaches to understand the proteins that recognize methylated DNA and certain modified histones, and to decipher their functions in gene expression and in the maintenance of genome stability. These approaches will include mass spectrometry to directly identify proteins and protein complexes able to bind to methylated DNA and methylated histones. The laboratory will also use Arabidopsis mutant screens to identify factors that act downstream of DNA methylation and various histone marks. A post translational modification of histones called H3K27 monomethylation is critical for repression of heterochromatin. In the absence of this mark, cells undergo both inappropriate gene expression and a massive DNA damage response resulting in amplification of heterochromatic DNA. A key part of the five-year plan will be to understand the mechanisms at play, and to understand the precise nature of the relationship between gene derepression and DNA damage.

项目摘要/摘要 我们的实验室重点是通过DNA甲基化和组蛋白的生物学和基因沉默的机制 修改主要使用拟南芥作为模型系统。最近的努力集中在 DNA甲基化适当地在基因组中构图的机制。主要发现是 由四个不同的DNA甲基转移酶驱动的四个不同的DNA甲基化途径作用于自我 加强在三种不同序列环境中维持胞嘧啶甲基化的机制，CG，CHG 和chh（其中h = a，t或c）。 DNA甲基化的建立由RNA指导控制 DNA甲基化途径和研究该途径一直是实验室的主要重点。最多 最近，实验室使用了遗传学，基因组学，蛋白质组学和结构生物学方法 表征了两个RNA聚合酶Pol IV和Pol V的机制，以产生非 - 对靶向RNA指导的DNA甲基化靶向特定基因座的编码RNA。来自 该实验室还将我们带入旨在了解下游行动的因素的新方向 DNA甲基化的既控制基因表达又保持基因组稳定性。在接下来的五个 几年，我们计划利用所有可用方法来了解识别甲基化的蛋白质 DNA和某些修饰的组蛋白，并在基因表达和 维持基因组稳定性。这些方法将包括质谱法以直接识别 蛋白质和蛋白质复合物能够与甲基化的DNA和甲基化组蛋白结合。实验室 还将使用拟南芥突变体筛选来识别DNA甲基化下游作用的因素和 各种组蛋白标记。称为H3K27单甲基化的组蛋白的翻译后修饰是 对于抑制异染色质至关重要。在没有此标记的情况下，细胞都经历了不适当的 基因表达和巨大的DNA损伤响应，导致异型DNA扩增。 五年计划的关键部分是了解发挥作用的机制，并了解 基因抑制与DNA损伤之间关系的精确性。

项目成果

DNA polymerase epsilon is required for heterochromatin maintenance in Arabidopsis.

• DOI: 10.1186/s13059-020-02190-1
• 发表时间: 2020-11-25
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Bourguet P;López-González L;Gómez-Zambrano Á;Pélissier T;Hesketh A;Potok ME;Pouch-Pélissier MN;Perez M;Da Ines O;Latrasse D;White CI;Jacobsen SE;Benhamed M;Mathieu O
• 通讯作者: Mathieu O

A SYBR Gold-based Label-free in vitro Dicing Assay.

基于 SYBR Gold 的无标记体外切割测定。

• DOI: 10.21769/bioprotoc.4382
• 发表时间: 2022
• 期刊: Bio-protocol
• 影响因子: 0.8
• 作者: Wang,Qian;Xue,Yan;Zhang,Laixing;Zhong,Zhenhui;Feng,Suhua;Wang,Changshi;Xiao,Lifan;Yang,Zhenlin;Harris,JakeC;Wu,Zhe;Zhai,Jixian;Yang,Maojun;Li,Sisi;Jacobsen,StevenE;Du,Jiamu
• 通讯作者: Du,Jiamu

Histone chaperone ASF1 mediates H3.3-H4 deposition in Arabidopsis.

组蛋白伴侣 ASF1 介导拟南芥中 H3.3-H4 沉积

• DOI: 10.1038/s41467-022-34648-0
• 发表时间: 2022-11-15
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Zhong, Zhenhui;Wang, Yafei;Wang, Ming;Yang, Fan;Thomas, Quentin Angelo;Xue, Yan;Zhang, Yaxin;Liu, Wanlu;Jami-Alahmadi, Yasaman;Xu, Linhao;Feng, Suhua;Marquardt, Sebastian;Wohlschlegel, James A.;Ausin, Israel;Jacobsen, Steven E.
• 通讯作者: Jacobsen, Steven E.

MBD2 couples DNA methylation to transposable element silencing during male gametogenesis.

• DOI: 10.1038/s41477-023-01599-3
• 发表时间: 2024-01
• 期刊: NATURE PLANTS
• 影响因子: 18
• 作者: Wang, Shuya;Wang, Ming;Ichino, Lucia;Boone, Brandon A.;Zhong, Zhenhui;Papareddy, Ranjith K.;Lin, Evan K.;Yun, Jaewon;Feng, Suhua;Jacobsen, Steven E.
• 通讯作者: Jacobsen, Steven E.

MORC proteins regulate transcription factor binding by mediating chromatin compaction in active chromatin regions.

• DOI: 10.1186/s13059-023-02939-4
• 发表时间: 2023-04-26
• 期刊: GENOME BIOLOGY
• 影响因子: 12.3
• 作者: Zhong, Zhenhui;Xue, Yan;Harris, C. Jake;Wang, Ming;Li, Zheng;Ke, Yunqing;Liu, Mukun;Zhou, Jessica;Jami-Alahmadi, Yasaman;Feng, Suhua;Wohlschlegel, James A.;Jacobsen, Steven E.
• 通讯作者: Jacobsen, Steven E.