Chromatin modifications and DNA methylation during early lung development
早期肺部发育过程中的染色质修饰和 DNA 甲基化
基本信息
- 批准号:7391424
- 负责人:
- 金额:$ 43.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-12-01 至 2012-11-30
- 项目状态:已结题
- 来源:
- 关键词:AntibodiesBindingBiological AssayBreedingCell Differentiation processCell LineageCellsChromatinChromatin Remodeling FactorCommitComplexDNADNA BindingDNA MethylationDNA Modification MethylasesDNA amplificationDeoxycytidineDevelopmentDominant-Negative MutationEZH2 geneEmbryoEndodermEpigenetic ProcessEpitheliumEvaluationFGFR2 geneGene ActivationGene ExpressionGene Expression RegulationGene TargetingGenesGenetic TranscriptionGenomeGenomicsGoalsHistonesIn VitroKnowledgeLentivirus VectorLinkLiverLungMesenchymeMessenger RNAMethylationMicroarray AnalysisModificationMusOrganOrganogenesisPatternPlayPolycombPost-Translational Protein ProcessingPrimitive foregut structurePrimordiumProteinsRNA Polymerase IIRegulationRoleSystemTestingTissuesUndifferentiatedbasebisulfitebrahmabrahma proteinchromatin immunoprecipitationchromatin remodelingdayembryonic stem cellenzyme activitygenetic regulatory proteinin vivolung developmentprogramspromoterprotein expressionrecombinasesmall hairpin RNAstem
项目摘要
The goal of this project is to investigate the role of chromatin modifications and DMA methylation in activation
or silencing of gene expression during initiation of lung development. Chromatin modifications and DNA
methylation in conjunction with DNA binding factors regulate transcription to achieve cell specific gene
expression. These mechanisms play a defined role in developmental programs, and have been shown to be
involved in the establishment of the specific cell lineages that will give rise to various organs, including
foregut derivatives such as the liver. Little is known about how these mechanisms influence gene
expression in the developing lung. In a microarray analysis of the developing foregut carried during the
previous period of this Program Project, we identified significant changes in the expression of genes
associated with chromatin remodeling and DNA methylation, coincident with the formation of the lung
primordium. The known important role of chromatin remodeling in cell fate decisions and differentiation led
us to hypothesize that chromatin remodeling and DNA methylation play a regulatory role in initiation of lung
development by establishing spatial and temporal patterns of gene expression in the embryonic foregut.
Thus we propose to: 1) identify changes in epigenetic modifications of selected lung gene promoters during
initiation of lung development in vivo and in cultured ES cells, 2) search for targets of activating chromatin
remodeling complexes in embryonic lung cells, 3) analyze the function of chromatin remodeling genes and
DNA methylation on the transcriptional activity of lung promoters in cells, and in wild type and genetically
modified lungs. The proposed studies include the characterization of chromatin modifications of lung gene
promoters by chromatin immunoprecipitation, DNA methylation and chromatin accessibility analyses in vitro
and in vivo, a global analysis of new targets of epigenetic gene activation, and the functional evaluation of
chromatin modification genes in lung gene development using foregut cultures and genetically modified
mice. Our findings will increase the knowledge of how the early patterns of lung expression are regulated in
vivo and in ES cells.
本项目的目标是研究染色质修饰和DNA甲基化在活化中的作用
或在肺发育起始期间基因表达的沉默。染色质修饰和DNA
甲基化与DNA结合因子共同调控转录,实现细胞特异性基因
表情这些机制在发育计划中发挥着明确的作用,并已被证明是
参与特定细胞谱系的建立,这些细胞谱系将产生各种器官,包括
前肠衍生物,如肝脏。关于这些机制如何影响基因,
在发育中的肺中表达。在一项对发育中的前肠的微阵列分析中,
在本计划项目的前一阶段,我们确定了基因表达的显著变化,
与染色质重塑和DNA甲基化相关,与肺的形成一致
原基染色质重塑在细胞命运决定和分化中的已知重要作用导致
我们假设染色质重塑和DNA甲基化在肺损伤的发生中起调节作用,
通过建立胚胎前肠中基因表达的空间和时间模式来研究胚胎发育。
因此,我们建议:1)确定在肺移植过程中所选肺基因启动子的表观遗传修饰的变化,
在体内和培养的ES细胞中启动肺发育,2)寻找激活染色质的靶点
3)分析染色质重塑基因的功能,
DNA甲基化对细胞中肺启动子转录活性的影响,以及在野生型和遗传型中的作用。
改良的肺拟议的研究包括肺基因的染色质修饰的表征
体外染色质免疫沉淀、DNA甲基化和染色质可及性分析
在体内,对表观遗传基因激活的新靶点进行了全面分析,并对表观遗传基因的功能进行了评估。
使用前肠培养物和遗传修饰的肺基因开发中的染色质修饰基因
小鼠我们的研究结果将增加对肺表达的早期模式如何调节的知识,
体内和ES细胞中。
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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Maria Isabel Ramirez其他文献
Maria Isabel Ramirez的其他文献
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{{ truncateString('Maria Isabel Ramirez', 18)}}的其他基金
Lung epithelial lineage-specific factors in the control of immune system evasion genes in tumor cells
肺上皮谱系特异性因子控制肿瘤细胞免疫系统逃避基因
- 批准号:
10201859 - 财政年份:2021
- 资助金额:
$ 43.91万 - 项目类别:
Lung epithelial lineage-specific factors in the control of immune system evasion genes in tumor cells
肺上皮谱系特异性因子控制肿瘤细胞免疫系统逃避基因
- 批准号:
10359835 - 财政年份:2021
- 资助金额:
$ 43.91万 - 项目类别:
Molecular and biological function of long non-coding RNA transcripts divergent to lung developmental genes
与肺发育基因不同的长非编码RNA转录物的分子和生物学功能
- 批准号:
8865010 - 财政年份:2015
- 资助金额:
$ 43.91万 - 项目类别:
Molecular and biological function of long non-coding RNA transcripts divergent to lung developmental genes
与肺发育基因不同的长非编码RNA转录物的分子和生物学功能
- 批准号:
9135496 - 财政年份:2015
- 资助金额:
$ 43.91万 - 项目类别:
Chromatin Modifications and DNA Methylation During Early Lung Development
早期肺发育过程中的染色质修饰和 DNA 甲基化
- 批准号:
8213816 - 财政年份:2011
- 资助金额:
$ 43.91万 - 项目类别:
Chromatin Modifications and DNA Methylation During Early Lung Development
早期肺发育过程中的染色质修饰和 DNA 甲基化
- 批准号:
8147553 - 财政年份:2010
- 资助金额:
$ 43.91万 - 项目类别:
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