Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects
控制颅面缺陷发生过程中环境污染物遗传易感性的蛋白质甲基化途径
基本信息
- 批准号:10277389
- 负责人:
- 金额:$ 42.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAblationAffectAnimal ModelAreaArginineAryl Hydrocarbon ReceptorBiochemicalBioinformaticsBlood VesselsCellular biologyChIP-seqCleft PalateComplexCongenital AbnormalityConnective TissueCraniofacial AbnormalitiesCuesDNA BindingDefectDeformityDepositionDevelopmentDifferentiation and GrowthDioxinsElementsEnvironmental PollutantsEnvironmental Risk FactorEnzymesEpigenetic ProcessExhibitsFaceGene ExpressionGenesGeneticGenetic ModelsGenetic Predisposition to DiseaseGenetic TranscriptionGenomicsGrowthHeadHistonesIncidenceInvestigationLigandsMandibleMapsMediatingMethylationMolecularMorphogenesisMusMuscleNerve TissueNeural Crest CellNuclear ReceptorsPalatePathway interactionsPredispositionPrevention strategyPrimordiumProcessProtein MethylationProtein-Arginine N-MethyltransferasePublic HealthResearchRiskRoleStressStructureTetrachlorodibenzodioxinToxic Environmental SubstancesToxic effectTranscriptional ActivationXenobioticsbone losscell behaviorcofactorcraniofacialcraniofacial bonecraniofacial developmentcraniumgene environment interactiongene inductionhigh risk populationimprovedliver injuryloss of functionmalformationmouse geneticsnon-histone proteinnovel strategiesnovel therapeuticsoxidative damagepalatal shelvespreventpupreceptorreceptor bindingresponsetranscriptometranscriptome sequencing
项目摘要
PROJECT SUMMARY / ABSTRACT
Formation of the head and face is a complex process that is highly susceptible to disturbance as evidenced by
the high incidence of craniofacial birth defects. Dysregulation in genetic and environmental factors are the main
causes of craniofacial defects. However, less than 50% of craniofacial defect cases have identified genetic
causes, and mechanisms of gene-environment interaction remains poorly understood. Therefore, molecular
investigation is needed to increase understanding of craniofacial development. We recently identified a new
regulator of craniofacial morphogenesis that interacts with environmental stress. This regulator, Protein
Arginine Methyltransferase 1 (PRMT1), is an enzyme that methylates histone to generate a transcriptional
activation mark H4R3me2a and methylation non-histone proteins on arginine residues. Prmt1 ablation in
neural crest cells caused cleft palate and skull malformation. We further uncovered a role for PRMT1 in
guarding against environmental toxin TCDD-induced cleft palate. In this proposal, we aim to determine
PRMT1-dependent transcription and epigenetic mechanisms that regulated TCDD-induced cellular changes
and developmental defects, using mouse genetic models, biochemical and cell biology approaches, RNA-seq,
ChIP-seq and bioinformatic analysis.
项目总结/摘要
头部和面部的形成是一个复杂的过程,非常容易受到干扰,如以下所示:
颅面出生缺陷的高发病率。遗传和环境因素的失调是主要的
颅面缺损的原因然而,不到50%的颅面缺陷病例已确定遗传性,
基因-环境相互作用的原因和机制仍然知之甚少。因此,分子
需要进行调查以增加对颅面发育的了解。我们最近发现了一种新的
与环境压力相互作用的颅面形态发生的调节器。这个调节器,蛋白质
精氨酸甲基转移酶1(PRMT 1)是一种使组蛋白甲基化以产生转录活性的酶。
激活标记H4 R3 me 2a和精氨酸残基上的甲基化非组蛋白蛋白。Prmt 1消融
神经嵴细胞引起腭裂和颅骨畸形。我们进一步揭示了PRMT 1在以下方面的作用:
预防环境毒素TCDD诱发腭裂。在本提案中,我们旨在确定
PRMT 1依赖的转录和表观遗传机制调节TCDD诱导的细胞变化
和发育缺陷,使用小鼠遗传模型,生物化学和细胞生物学方法,RNA-seq,
ChIP-seq和生物信息学分析。
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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Jian Xu其他文献
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{{ truncateString('Jian Xu', 18)}}的其他基金
Elucidating the Functional and Mechanistic Roles of LINE-1 Retrotransposons in Myeloid Leukemia
阐明 LINE-1 逆转录转座子在髓系白血病中的功能和机制作用
- 批准号:
10380514 - 财政年份:2021
- 资助金额:
$ 42.66万 - 项目类别:
Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects
控制颅面缺陷发生过程中环境污染物遗传易感性的蛋白质甲基化途径
- 批准号:
10651798 - 财政年份:2021
- 资助金额:
$ 42.66万 - 项目类别:
Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects
控制颅面缺陷发生过程中环境污染物遗传易感性的蛋白质甲基化途径
- 批准号:
10436980 - 财政年份:2021
- 资助金额:
$ 42.66万 - 项目类别:
Elucidating the Functional and Mechanistic Roles of LINE-1 Retrotransposons in Myeloid Leukemia
阐明 LINE-1 逆转录转座子在髓系白血病中的功能和机制作用
- 批准号:
10532726 - 财政年份:2021
- 资助金额:
$ 42.66万 - 项目类别:
Elucidating the transcriptional mechanisms that control the expression of the SARS-CoV-2 receptor ACE2
阐明控制 SARS-CoV-2 受体 ACE2 表达的转录机制
- 批准号:
10179069 - 财政年份:2021
- 资助金额:
$ 42.66万 - 项目类别:
Elucidating the Functional and Mechanistic Roles of LINE-1 Retrotransposons in Myeloid Leukemia
阐明 LINE-1 逆转录转座子在髓系白血病中的功能和机制作用
- 批准号:
10860830 - 财政年份:2021
- 资助金额:
$ 42.66万 - 项目类别:
Targeting Metabolic Liabilities of Leukemia-Initiating Cells
针对白血病起始细胞的代谢能力
- 批准号:
10551337 - 财政年份:2019
- 资助金额:
$ 42.66万 - 项目类别:
Targeting Metabolic Liabilities of Leukemia-Initiating Cells
针对白血病起始细胞的代谢能力
- 批准号:
10331858 - 财政年份:2019
- 资助金额:
$ 42.66万 - 项目类别:
Targeting Metabolic Liabilities of Leukemia-Initiating Cells (R01CA230631)
针对白血病起始细胞的代谢能力 (R01CA230631)
- 批准号:
10865405 - 财政年份:2019
- 资助金额:
$ 42.66万 - 项目类别:
Modulation of Runx2 activity by arginine methylation
通过精氨酸甲基化调节 Runx2 活性
- 批准号:
9903272 - 财政年份:2019
- 资助金额:
$ 42.66万 - 项目类别:
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