Breaking Nucleosomal Symmetry
打破核小体对称性
基本信息
- 批准号:8892203
- 负责人:
- 金额:$ 31.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-15 至 2018-04-30
- 项目状态:已结题
- 来源:
- 关键词:AffectBiochemicalBiochemistryBiological ProcessCellsChromatinChromosomesDefectDependencyEnzymesEukaryotaEventExhibitsGene ExpressionGene Expression RegulationGenesGeneticGenetic EpistasisGenetic studyGenomicsGrowthHealthHistone H3HistonesHumanLifeMalignant NeoplasmsMass Spectrum AnalysisMeasuresMessenger RNAMethodsModificationMolecular GeneticsMutateMutationNucleosomesPathway interactionsPatternPhenotypePlayPoint MutationProteinsRoleSaccharomycetalesSiteSystemTailTestingTimeWorkYeastsabstractingbasedesigngenome-widehistone modificationhuman diseasein vivoinsightinterdisciplinary approachmanmutantnovelprotein structure predictionpublic health relevanceresearch studyresponsestoichiometry
项目摘要
DESCRIPTION (provided by applicant):
Project Summary / Abstract We have developed methods to manipulate for the first time the natural symmetry of nucleosomes, in order to test the extent to which this symmetry is functionally important. These questions cannot be pursued in cells with natural histones. Therefore, we have designed altered histone H3s that have obligate heterodimeric interactions, and which preclude interaction with wild-type H3 molecules. We will now use these altered H3s to measure how nucleosomal asymmetry affects gene expression and histone modification patterns, as follows: Aim 1. Identify the mechanistic basis for epistatic interactions between histone tails. In our preliminary studies, we observed distinct classes of phenotypes upon mutation of modifiable residues: in one case, a single asymmetric H3 point mutation paired with a wild-type partner exhibited all the transcriptional defects of a double point mutant. In another case, genes were only misregulated in symmetric double mutants. We will extend these studies to a large set of histone mutations to understand the mechanistic basis for the epistasis observed between pairs of histone mutants. Aim 2. Determine whether histone crosstalk functions in cis or in trans. A great number of histone modifying enzymes preferentially act on nucleosomes carrying some second modification, a phenomenon often referred to as "cross-talk". We will use genetic and biochemical approaches to assess whether crosstalk occurs in cis, on the same tail, or in trans, on opposite tails: we will identify the quantitative difference in gene expression between cells with cis and trans double K->R mutations in the H3 tail, and perform mass spectrometric analysis of purified asymmetric nucleosomes to determine whether second site modifications are lost in cis, in trans, or are unaffected by monomeric histone mutations. Together, these studies will reveal previously unexplored biochemical dependency pathways that alter histone modification patterns, and distinguish gene expression regulatory events that are dependent on one versus two histone H3 N-termini. Notably, because of the extreme conservation of core histones among eukaryotes, this work will open the way to exploring related questions in metazoans. Because histone modifications are central to all aspects of gene expression from yeast to man, and play major roles in human diseases including cancer, these studies will reveal unappreciated regulatory mechanisms that govern human health and growth control.
描述(由申请人提供):
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
PAUL D. KAUFMAN其他文献
PAUL D. KAUFMAN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('PAUL D. KAUFMAN', 18)}}的其他基金
FASEB SRC: The Nuclear Bodies Conference: Hubs of Genomic Activity
FASEB SRC:核机构会议:基因组活动中心
- 批准号:
10467741 - 财政年份:2022
- 资助金额:
$ 31.39万 - 项目类别:
Eukaryotic Nuclear Functions: from Nucleosomes to Chromosomes
真核生物核功能:从核小体到染色体
- 批准号:
10152614 - 财政年份:2018
- 资助金额:
$ 31.39万 - 项目类别:
Eukaryotic Nuclear Functions: from Nucleosomes to Chromosomes
真核生物核功能:从核小体到染色体
- 批准号:
10400845 - 财政年份:2018
- 资助金额:
$ 31.39万 - 项目类别:
Eukaryotic Nuclear Functions: from Nucleosomes to Chromosomes
真核细胞核功能:从核小体到染色体
- 批准号:
9923723 - 财政年份:2018
- 资助金额:
$ 31.39万 - 项目类别:
Nucleolar Genomics During Early Mammalian Development
哺乳动物早期发育过程中的核仁基因组学
- 批准号:
9326974 - 财政年份:2015
- 资助金额:
$ 31.39万 - 项目类别:
Nucleolar Genomics During Early Mammalian Development
哺乳动物早期发育过程中的核仁基因组学
- 批准号:
9764307 - 财政年份:2015
- 资助金额:
$ 31.39万 - 项目类别:
IDENTIFICATION OF PROTEINS THAT REGULATE THE SIN3A HISTONE DEACETYLASE COMPLEX
调节 SIN3A 组蛋白脱乙酰酶复合物的蛋白质的鉴定
- 批准号:
8171342 - 财政年份:2010
- 资助金额:
$ 31.39万 - 项目类别:
IDENTIFICATION OF PROTEINS THAT REGULATE THE SIN3A HISTONE DEACETYLASE COMPLEX
调节 SIN3A 组蛋白脱乙酰酶复合物的蛋白质的鉴定
- 批准号:
7957764 - 财政年份:2009
- 资助金额:
$ 31.39万 - 项目类别:
相似海外基金
CAREER: Biochemical and Structural Mechanisms Controlling tRNA-Modifying Metalloenzymes
职业:控制 tRNA 修饰金属酶的生化和结构机制
- 批准号:
2339759 - 财政年份:2024
- 资助金额:
$ 31.39万 - 项目类别:
Continuing Grant
Leveraging releasable aryl diazonium ions to probe biochemical systems
利用可释放的芳基重氮离子探测生化系统
- 批准号:
2320160 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Standard Grant
Diurnal environmental adaptation via circadian transcriptional control based on a biochemical oscillator
基于生化振荡器的昼夜节律转录控制的昼夜环境适应
- 批准号:
23H02481 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Systematic manipulation of tau protein aggregation: bridging biochemical and pathological properties
tau 蛋白聚集的系统操作:桥接生化和病理特性
- 批准号:
479334 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Operating Grants
Converting cytoskeletal forces into biochemical signals
将细胞骨架力转化为生化信号
- 批准号:
10655891 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Enhanced Biochemical Monitoring for Aortic Aneurysm Disease
加强主动脉瘤疾病的生化监测
- 批准号:
10716621 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Biochemical Mechanisms for Sustained Humoral Immunity
持续体液免疫的生化机制
- 批准号:
10637251 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Structural and biochemical investigations into the mechanism and evolution of soluble guanylate cyclase regulation
可溶性鸟苷酸环化酶调节机制和进化的结构和生化研究
- 批准号:
10604822 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Chemical strategies to investigate biochemical crosstalk in human chromatin
研究人类染色质生化串扰的化学策略
- 批准号:
10621634 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Examination of risk assessment and biochemical assessment of fracture development focusing on the body composition of patients with rheumatoid arthritis
关注类风湿性关节炎患者身体成分的骨折发生风险评估和生化评估检查
- 批准号:
22KJ2600 - 财政年份:2023
- 资助金额:
$ 31.39万 - 项目类别:
Grant-in-Aid for JSPS Fellows