Histone Demethylase Control of Post Implantation Development
组蛋白去甲基化酶对植入后发育的控制
基本信息
- 批准号:10596098
- 负责人:
- 金额:$ 38.94万
- 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:2022-04-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:AdenosineAffectArginineCell NucleusCellsChromatinCuesCytosineDNADNA MethylationDataDefectDependenceDevelopmentElementsEnabling FactorsEnvironmentEnzymesEpiblastEpigenetic ProcessEventExcisionFamilyFertilizationGene ExpressionGene Expression ProfileGene SilencingGenesGeneticGenomeGerm CellsGonadal structureHistonesImmunofluorescence ImmunologicInfertilityLocationLysineMeasuresMediatingMessenger RNAMethodsMethylationMethyltransferaseModificationMusNuclear TranslocationOrganismPatternPhenotypePlayPost-Transcriptional RegulationProteinsRNARNA SplicingRepetitive SequenceReportingRepressionRoleSeriesSignal TransductionSpecific qualifier valueStructure of primordial sex cellTestingTetanus Helper PeptideTissuesTotipotentactive controlarginine methyltransferasecell motilitychromatin immunoprecipitationdemethylationdesigndevelopmental diseaseembryonic stem cellepigenetic regulationepitranscriptomeepitranscriptomicsgenome integritygenome-widegenomic locushistone demethylasehistone modificationimplantationimprintin vitro Modelin vivoinsightmigrationnon-geneticposttranscriptionalpreventprotein complexrecruittranscription factortranscriptometransgenerational epigenetic inheritancetransmission processzygote
项目摘要
ABSTRACT
Functional specialization in a multicellular organism arises when cell fate is established by a specific gene
expression pattern. Epigenetic modifications working with transcription factors enable cell identity. During early
development a few cells migrate at the epiblast stage to the gonad to become Primordial germ cells (PGCs),
which are the precursors of gametes. PGCs undergo an ordered series of global epigenetic changes that
decimates the repressive modifications: H3 lysine 9 methylation (H3K9me2) and DNA methylation, which
suppress expression of repetitive elements to maintain genomic integrity, and is replaced by other marks such
as H2A/H4 arginine methylation (H2A/H4R3me2). How the precise temporal regulation of these epigenetic
events is coordinated and their interdependence remains poorly understood. Incorrect or partial erasure at
specific locations could lead to imprinting defects as well as inadvertent transgenerational inheritance. We
have discovered that the H3K9me2 demethylase, KDM3B, controls DNA demethylation by the Tet enzymes
and interacts with PRMT5, a H2A/H4R3 methyltransferase. Despite H3K9me2 being a repressive histone
modification, we have found that KDM3B and KDM3A interact with mRNA processing machinery. Taken
together we hypothesize that proteins of the KDM3 family orchestrate post-implantation development to PGCs
by epigenetic and post-transcriptional mechanisms, which will be investigated in this proposal.
摘要
当细胞命运由特定基因决定时,多细胞生物的功能特化就产生了
表达模式与转录因子一起工作的表观遗传修饰使细胞身份成为可能。早期
在发育过程中,少数细胞在上胚层阶段迁移到性腺成为原始生殖细胞(PGCs),
它们是配子的前体PGCs经历一系列有序的整体表观遗传变化,
减少了抑制性修饰:H3赖氨酸9甲基化(H3 K9 me 2)和DNA甲基化,
抑制重复元件的表达以维持基因组的完整性,并被其他标记所取代,
如H2 A/H4精氨酸甲基化(H2 A/H4 R3 me 2)。这些表观遗传的精确时间调节
这些事件是协调的,它们的相互依存关系仍然不为人所知。错误或部分擦除.
特定的位置可能会导致印记缺陷以及无意中的跨代遗传。我们
已经发现H3 K9 me 2脱甲基酶KDM 3B通过泰特酶控制DNA脱甲基化
并与PRMT 5(H2 A/H4 R3甲基转移酶)相互作用。尽管H3 K9 me 2是一种抑制性组蛋白,
通过修饰,我们发现KDM 3B和KDM 3A与mRNA加工机制相互作用。采取
我们共同假设KDM 3家族的蛋白质协调着床后发育为PGC
通过表观遗传和转录后机制,这将在本提案中进行研究。
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)
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Rupa Sridharan其他文献
Rupa Sridharan的其他文献
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{{ truncateString('Rupa Sridharan', 18)}}的其他基金
Histone Demethylase Control of Post Implantation Development
组蛋白去甲基化酶对植入后发育的控制
- 批准号:
10367127 - 财政年份:2022
- 资助金额:
$ 38.94万 - 项目类别:
Collaboration of chromatin remodeling and signaling pathways in pluripotency
染色质重塑和多能性信号通路的协作
- 批准号:
9281756 - 财政年份:2015
- 资助金额:
$ 38.94万 - 项目类别:
Collaboration of chromatin remodeling and signaling pathways in pluripotency
多能性中染色质重塑和信号通路的协作
- 批准号:
8973055 - 财政年份:2015
- 资助金额:
$ 38.94万 - 项目类别:
Collaboration of chromatin remodeling and signaling pathways in pluripotency
多能性中染色质重塑和信号通路的协作
- 批准号:
10677665 - 财政年份:2015
- 资助金额:
$ 38.94万 - 项目类别:
R01 Renewal: Collaboration of chromatin remodeling and signaling pathways in pluripotency
R01 更新:染色质重塑和多能性信号通路的协作
- 批准号:
10798738 - 财政年份:2015
- 资助金额:
$ 38.94万 - 项目类别:
Collaboration of chromatin remodeling and signaling pathways in pluripotency
多能性中染色质重塑和信号通路的协作
- 批准号:
9108412 - 财政年份:2015
- 资助金额:
$ 38.94万 - 项目类别:
Collaboration of chromatin remodeling and signaling pathways in pluripotency
多能性中染色质重塑和信号通路的协作
- 批准号:
9973438 - 财政年份:2015
- 资助金额:
$ 38.94万 - 项目类别:
Collaboration of chromatin remodeling and signaling pathways in pluripotency
多能性中染色质重塑和信号通路的协作
- 批准号:
10456061 - 财政年份:2015
- 资助金额:
$ 38.94万 - 项目类别:
Collaboration of chromatin remodeling and signaling pathways in pluripotency
多能性中染色质重塑和信号通路的协作
- 批准号:
10225525 - 财政年份:2015
- 资助金额:
$ 38.94万 - 项目类别:
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