Histone Acetylation Dynamics and Epigenome Duplication
组蛋白乙酰化动力学和表观基因组复制
基本信息
- 批准号:10343912
- 负责人:
- 金额:$ 40.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-03 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAcetylationArchitectureCell MaintenanceCell NucleusCell divisionCellsChromatinChromatin StructureComplexDNADNA Modification ProcessDNA SequenceDNA StructureDNA biosynthesisDNA replication forkDataDaughterDefectDepositionEpigenetic ProcessEukaryotaGene ExpressionGenesGenetic TranscriptionGenomeGenome StabilityGenomic DNAGoalsHAT1 geneHeterochromatinHistone AcetylationHistone H3Histone H4HistonesKnowledgeLaboratoriesLaminsLinkLocationMammalian CellMethylationModelingModificationMolecular GeneticsNuclearNuclear LaminaNucleosomesOutcomePathway interactionsPatternPhenocopyPlayPost-Translational Protein ProcessingProteinsRegulationResearchRoleS phaseSolidStructureTherapeuticWorkbasechromatin modificationdensityepigenomeepigenomicsexperimental studygenetic approachhistone acetyltransferasehistone modificationhuman diseaseinfancyinnovationinsightmammalian genomenon-histone proteinpreservationprogramsrestorationspatial memorythree dimensional structure
项目摘要
Eukaryotic genomes exist in a complex and dynamic 3-dimensional structure that provides important regulatory
information controlling gene expression programs essential for the maintenance of cell identity. Genome
structure is also critical for packaging the genome in the nucleus and preserving genome stability. Genome
structure is primarily dictated by its' association with the histone proteins to form chromatin. The post-
translational modifications on histones play a key role in determining genome structure as they regulate the
association of non-histone proteins with genomic DNA. An important challenge for eukaryotes is the
epigenetic inheritance of the histone modification patterns that govern genome structure following DNA
replication and cell division. This proposal seeks to identify fundamental mechanisms that regulate the
epigenetic inheritance of histone modification patterns.
Following passage of a replication fork, newly replicated DNA is packaged into chromatin that contains a 1:1
mixture of parental histones and newly synthesized histones. The retention of modification patterns on
parental histones provides the spatial memory for the duplication of specific chromatin states. The key step in
epigenetic inheritance is the transfer of the parental modification patterns to the neighboring new histones.
Our work is based on the hypothesis that the new histones play a critical regulatory role in the epigenetic
inheritance of chromatin states. The current proposal is based on my lab's identification of previously unknown
links between the dynamic acetylation of newly synthesized histones and the epigenetic inheritance of specific
chromatin states and the restoration of 3-dimensional genome architecture following DNA replication. The
experiments proposed here will characterize the effect of new histone acetylation on the structure and
composition of chromatin and identify factors and pathways that function with new histone acetylation to
regulate the epigenetic inheritance of chromatin states. In addition, we will characterize a previously
unanticipated role of new histone acetylation in the epigenetic inheritance of 3-dimensional genome
architecture through regulation of the interactions between chromatin and the nuclear lamina.
真核生物基因组存在于一个复杂的和动态的三维结构,提供了重要的调控
控制基因表达程序的信息,这些程序对维持细胞身份至关重要。基因组
结构对于在细胞核中包装基因组和保持基因组稳定性也是至关重要的。基因组
结构主要由其与组蛋白结合形成染色质决定。邮报-
组蛋白的翻译修饰在决定基因组结构方面发挥着关键作用,因为它们调节基因组结构。
非组蛋白与基因组DNA的关联。真核生物面临的一个重要挑战是
组蛋白修饰模式的表观遗传,该模式控制DNA后的基因组结构
复制和细胞分裂。该提案旨在确定规范这些活动的基本机制,
组蛋白修饰模式的表观遗传。
在复制叉通过后,新复制的DNA被包装到含有1:1 DNA的染色质中。
亲本组蛋白和新合成的组蛋白的混合物。修改模式的保留
亲本组蛋白为特定染色质状态的复制提供空间记忆。的关键步骤
表观遗传是亲本修饰模式转移到邻近的新组蛋白。
我们的工作是基于这样的假设,即新的组蛋白在表观遗传中起着关键的调节作用,
染色质状态的遗传。目前的建议是基于我的实验室对以前未知的
新合成的组蛋白的动态乙酰化与特异性的表观遗传之间的联系
染色质状态和DNA复制后三维基因组结构的恢复。的
这里提出的实验将表征新的组蛋白乙酰化对结构的影响,
染色质的组成,并确定与新的组蛋白乙酰化,
调节染色质状态的表观遗传。此外,我们将描述一个以前
新组蛋白乙酰化在三维基因组表观遗传中的意想不到的作用
通过调节染色质和核纤层之间的相互作用来调节核结构。
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 }}
MARK R PARTHUN其他文献
MARK R PARTHUN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('MARK R PARTHUN', 18)}}的其他基金
Histone Acetylation Dynamics and Epigenome Duplication
组蛋白乙酰化动力学和表观基因组复制
- 批准号:
10561721 - 财政年份:2022
- 资助金额:
$ 40.77万 - 项目类别:
Type B Histone Acetyltransferases and the Assembly of Chromatin Structure
B 型组蛋白乙酰转移酶和染色质结构的组装
- 批准号:
7921242 - 财政年份:2009
- 资助金额:
$ 40.77万 - 项目类别:
Histone Modification and Changes in Chromatin: Silencing of Tumor Suppressor Gene
组蛋白修饰和染色质变化:肿瘤抑制基因的沉默
- 批准号:
6986005 - 财政年份:2005
- 资助金额:
$ 40.77万 - 项目类别:
Characterization of Type B Histone Acetyltransferases
B 型组蛋白乙酰转移酶的表征
- 批准号:
6520469 - 财政年份:2001
- 资助金额:
$ 40.77万 - 项目类别:
Type B Histone Acetyltransferases and the Assembly of Chromatin Structure
B 型组蛋白乙酰转移酶和染色质结构的组装
- 批准号:
8629759 - 财政年份:2001
- 资助金额:
$ 40.77万 - 项目类别:
Type B histone acetyltransferases and the assembly of chromatin structure
B型组蛋白乙酰转移酶和染色质结构的组装
- 批准号:
8887576 - 财政年份:2001
- 资助金额:
$ 40.77万 - 项目类别:
Characterization of Type B Histone Acetyltransferases
B 型组蛋白乙酰转移酶的表征
- 批准号:
6636629 - 财政年份:2001
- 资助金额:
$ 40.77万 - 项目类别:
Type B Histone Acetyltransferases and the Assembly of Chromatin Structure
B 型组蛋白乙酰转移酶和染色质结构的组装
- 批准号:
7252463 - 财政年份:2001
- 资助金额:
$ 40.77万 - 项目类别:
Type B Histone Acetyltransferases and the Assembly of Chromatin Structure
B 型组蛋白乙酰转移酶和染色质结构的组装
- 批准号:
7145376 - 财政年份:2001
- 资助金额:
$ 40.77万 - 项目类别:
Characterization of Type B Histone Acetyltransferases
B 型组蛋白乙酰转移酶的表征
- 批准号:
6895241 - 财政年份:2001
- 资助金额:
$ 40.77万 - 项目类别:
相似海外基金
Investigating the functions of histone acetylation in genome organization and leukemogenesis
研究组蛋白乙酰化在基因组组织和白血病发生中的功能
- 批准号:
EP/Y000331/1 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
Research Grant
Gene Modulation of Acetylation Modifiers to Reveal Regulatory Links to Human Cardiac Electromechanics
乙酰化修饰剂的基因调节揭示与人类心脏机电的调节联系
- 批准号:
10677295 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
Novel roles of PDK2 in heart failure: Regulation of mitochondrial nuclear crosstalk via metabolic regulation and histone acetylation
PDK2 在心力衰竭中的新作用:通过代谢调节和组蛋白乙酰化调节线粒体核串扰
- 批准号:
10635599 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
Regulation of hepatic lysine N-acetylation by cysteine proximity due to alcohol toxicity
酒精毒性导致的半胱氨酸接近对肝脏赖氨酸 N-乙酰化的调节
- 批准号:
10752320 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
Histone Acetylation Regulates Microglial Innate Immune Memory
组蛋白乙酰化调节小胶质细胞先天免疫记忆
- 批准号:
478927 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
Operating Grants
Dysregulation of Histone Acetylation in Parkinson's Disease
帕金森病中组蛋白乙酰化的失调
- 批准号:
10855703 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
Obesity-related hypertension: the contribution of PPAR gamma acetylation and asprosin
肥胖相关高血压:PPAR γ 乙酰化和白脂素的贡献
- 批准号:
10654210 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
The role N-terminal acetylation in dilated cardiomyopathy and associated arrhythmia
N-末端乙酰化在扩张型心肌病和相关心律失常中的作用
- 批准号:
10733915 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
In vivo tracing of hepatic ethanol metabolism to histone acetylation: role of ACSS2 in alcohol-induced liver injury
肝脏乙醇代谢与组蛋白乙酰化的体内追踪:ACSS2 在酒精性肝损伤中的作用
- 批准号:
10667952 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别:
The function of TWIST1 acetylation in cell fate and tissue development
TWIST1 乙酰化在细胞命运和组织发育中的作用
- 批准号:
10726986 - 财政年份:2023
- 资助金额:
$ 40.77万 - 项目类别: