The function of a single-component chromatin remodeling protein Fun30 in vivo

单组分染色质重塑蛋白 Fun30 的体内功能

• 批准号: 8291024
• 负责人: Wei-Hua E Wu
• 金额: $ 15.24万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8291024
• 关键词: ATP phosphohydrolase; Biochemical; Biological; Biological Models; Biological Process; Camptothecin; Cells; Chromatin; Chromatin Remodeling Factor; Chromosomes; DNA; DNA Damage; DNA Microarray Chip; DNA Repair; DNA biosynthesis; Defect; Disease; Event; Exhibits; Failure; Gene Expression; Gene Targeting; Genetic; Genetic Transcription; Genome Stability; Genomic Instability; Goals; Histone H2A; Homologous Gene; Human; Kinetics; Lead; Malignant Neoplasms; Maps; Mediating; Metabolism; Molecular Biology; Normal Cell; Nuclear; Nucleosomes; Oligonucleotide Probes; Phenotype; Physiologic pulse; Physiological; Positioning Attribute; Process; Proteins; Regulation; Research; Research Personnel; Saccharomyces cerevisiae; Slide; Techniques; Variant; Work; Yeasts; cancer cell; chromatin remodeling; density; genome wide association study; genome-wide; hydroxyurea; in vitro activity; in vivo; insight; mutant; overexpression; programs; recombinational repair; response

DESCRIPTION (provided by applicant): ATP-dependent chromatin remodeling is a key regulatory component of nuclear events, such as DNA replication, repair, recombination and transcription. Misregulation of these events can lead to disordered gene expression, failed DNA damage response and subsequent genome instability, all of which are major causes of human cancer. The long-term objective of my research is to understand how chromatin remodeling regulates these events and how this regulation may be altered in cancer cells. We have identified a single-component chromatin remodeling factor previously designated as Fun30 in yeast. Deletion of yeast FUN30 renders cells sensitive to DNA damaging agents. Overexpression of FUN30 or its human homolog has been implicated in causing genome instability. Biochemical studies show that Fun30 exhibits an ATP-dependent nucleosome sliding activity. However, little is known about the chromatin remodeling function of Fun30 in vivo. We hypothesize that the ATP dependent chromatin remodeling by Fun30 regulates nucleosome positioning in vivo. Using the yeast Saccharomyces cerevisiae as model system and the state-of-the-art techniques, we propose to: 1) Determine the chromatin remodeling function of Fun30 by chromosome-wide mapping of changes in Fun30 dependent nucleosome positioning. 2) Determine the biological targets of Fun30 by genome-wide mapping of Fun30 localization using high density ChlP-chip. 3) Functional analysis of Fun30 at its target genes. The successful completion of these studies will provide the first genome-wide examination of nucleosome positioning regulated by ATP-dependent chromatin remodeling. It will also provide insight into the functional significance of Fun30 mediated chromatin remodeling for transcription and other nuclear events.

描述（由申请人提供）：ATP依赖性染色质重塑是核事件（如DNA复制、修复、重组和转录）的关键调控组分。这些事件的错误调节可导致基因表达紊乱、DNA损伤反应失败和随后的基因组不稳定性，所有这些都是人类癌症的主要原因。我研究的长期目标是了解染色质重塑如何调节这些事件以及这种调节如何在癌细胞中改变。我们已经确定了一个单组分染色质重塑因子先前指定为Fun30在酵母中。酵母FUN30的缺失使细胞对DNA损伤剂敏感。FUN30或其人类同源物的过表达涉及引起基因组不稳定性。生化研究表明Fun30具有ATP依赖的核小体滑动活性。然而，对Fun30在体内的染色质重塑功能知之甚少。我们推测Fun30通过ATP依赖的染色质重塑调节体内核小体定位。本研究以酿酒酵母为模型系统，采用最先进的技术手段：1）通过Fun30依赖性核小体定位的全染色体定位，确定Fun30的染色质重塑功能。 2)通过使用高密度ChIP芯片的Fun30定位的全基因组定位来确定Fun30的生物学靶标。 3)Fun30靶基因的功能分析这些研究的成功完成将提供第一个全基因组检查的核小体定位调节ATP依赖的染色质重塑。它还将提供深入了解Fun30介导的染色质重塑对转录和其他核事件的功能意义。

项目成果

Role of the ATP-dependent chromatin remodeling enzyme Fun30/Smarcad1 in the regulation of mRNA splicing.

ATP 依赖性染色质重塑酶 Fun30/Smarcad1 在 mRNA 剪接调节中的作用。

• DOI: 10.1016/j.bbrc.2020.02.175
• 发表时间: 2020
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Niu,Qiankun;Wang,Wei;Wei,Zhe;Byeon,Boseon;Das,AsimBikas;Chen,Bo-Shiun;Wu,Wei-Hua
• 通讯作者: Wu,Wei-Hua