Runx1 Binding Sites as Scaffolds That Mediate Chromosome Translocation
Runx1 结合位点作为介导染色体易位的支架
基本信息
- 批准号:7324069
- 负责人:
- 金额:$ 3.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-12-01 至 2009-11-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcuteAcute Myelocytic LeukemiaAddressArchitectureAreaBindingBinding SitesBiochemicalBiologicalBiological AssayBiological ModelsBone TissueCCAAT-Enhancer-Binding ProteinsCalvariaCell NucleusCellsCharacteristicsChileChromatinChromatin StructureChromosomal translocationChromosome TerritoryChromosomesChromosomes, Human, Pair 21CollaborationsComplexConditionCoupledCouplingCuesDNADNA Double Strand BreakDNA SequenceDNA-Binding ProteinsDataDetectionDevelopmentDiseaseElementsEmployee StrikesEventExperimental DesignsFetal DevelopmentFluorescence MicroscopyFrequenciesFutureGene ActivationGene ExpressionGene TargetingGenerationsGenesGeneticGenetic RecombinationGenetic TranscriptionGenomicsGoalsGrantHematopoieticHistone H4HistonesHormone ResponsiveHuman CharacteristicsHypersensitivityIn SituIntronsLaboratoriesLeadLifeLinkLocationMediatingMethodsModificationMolecularMolecular ConformationMolecular StructureMonitorMusMutationNuclearNuclear EnvelopeNuclear MatrixNuclear StructureNucleosomesOsteoblastsOsteocalcinOsteogenesisPatternPhysiologicalPositioning AttributePost-Translational Protein ProcessingPredisposing FactorPredispositionProcessProtein DynamicsProteinsPsyche structureRUNX1 geneRecombinantsRecruitment ActivityRegulatory ElementResearchRoleSkeletal DevelopmentSkeletal systemStagingStructureSusceptibility GeneTestingTrans-ActivatorsTranscriptional ActivationTranscriptional RegulationTransgenesUnited States National Institutes of HealthVitamin DWorkbasebonechromatin remodelingchronic leukemiacofactorgenetic regulatory proteinin vivoinsightmutantnovelnucleaseparent grantpreventprogramspromoterresearch studyresponsescaffoldsteroid hormonet(821)(q22q22)tooltranscription factor
项目摘要
A striking characteristic of the human acute and chronic leukemias is the finding that they are the result of
nonrandom, somatically acquired chromosomal translocations. The long-term goal of our research is to
determine if there is a common mechanism involved in the generation of chromosomal translocations. As a
biological model, we are using the RUNX1 gene, which encodes an important hematopoietic transcription
factor and is the most frequent target of chromosomal translocations in acute myeloid leukemia (AMI). The
RUNX1 gene is located on chromosome 21, and interestingly, for both the (8; 21) and (16; 21) AML-related
translocations, all the genomic breakpoints are found in intron 5. Therefore, a key question is what are the
factors that predispose the RUNX1 gene to be involved in chromosomal translocations? Our working
hypothesis is that the chromatin structure present at the breakpoint regions is determinant for the t(8;21)
translocation. Moreover, we hypothesize that the sub-nuclear localization of a gene may be determinant
both of the gene susceptibility to dsDNA breaks and in the selection of the partner gene when a translocation
is generated. A detailed comparison between the structural characteristics of chromatin and the nuclear
positioning of the RUNX1, ETO and the recombinant AML/ETO locus will allow us to identify the presence of
common features that may account for the increased accessibility observed at the breakpoint regions. The
proposed experiments based on our preliminary data will combine the expertise of the collaborating
laboratories to investigate the cis and trans acting factors that can be determinants of the RUNX1 locus
recombination frequency. The focus of the parent grant is the interrelationship between chromatin
organization, nuclear compartmentalization of Runx factors, and gene expression. In this FIRCA proposal,
we extend the scope of these studies to address the relationship between Runx regulatory factors, nuclear
localization, and susceptibility to chromosomal translocations. This research will be done primarily in Chile at
the Universidad de Concepcion in collaboration with Soraya Gutierrez, as an extension of NIH grant 5P01
AR48818, projects.
人类急性和慢性白血病的一个显著特征是发现它们是由
非随机的体细胞获得性染色体易位。我们研究的长期目标是
确定染色体易位的产生是否有共同的机制。作为一名
生物模型,我们使用的是RUNX1基因,它编码一种重要的造血转录
是急性髓系白血病(AMI)最常见的染色体易位靶点。这个
RUNX1基因位于21号染色体上,有趣的是,与(8;21)和(16;21)AML相关的
易位,所有的基因组断裂点都在内含子5中被发现。因此,一个关键的问题是什么是
使RUNX1基因参与染色体易位的因素?我们的工作
假设存在于断点区的染色质结构是t(8;21)的决定因素。
易位。此外,我们假设基因的亚核定位可能是决定性的。
对dsDNA断裂的易感性和易位时伴侣基因的选择
是生成的。染色质与细胞核结构特征的详细比较
定位RUNX1、ETO和重组的AML/ETO基因座将使我们能够识别
可以解释在断点区域观察到的可访问性增加的共同特征。这个
根据我们的初步数据提出的实验将结合合作的专业知识
实验室研究可作为RUNX1基因座决定因素的顺式和反式作用因素
重组频率。母基金的重点是染色质之间的相互关系。
组织、RUNX因子的核区划和基因表达。在FIRCA的这份提案中,
我们扩大了这些研究的范围,以解决RUNX调控因素、核
定位和对染色体易位的易感性。这项研究将主要在智利进行,时间为
康塞普西翁大学与索拉亚·古铁雷斯合作,作为NIH赠款5P01的延伸
AR48818,项目。
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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Janet L Stein其他文献
Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression
Runx2 对骨骼基因表达调控机制的组织、组装和活性的控制
- DOI:
10.1038/sj.onc.1207676 - 发表时间:
2004-05-24 - 期刊:
- 影响因子:7.300
- 作者:
Gary S Stein;Jane B Lian;Andre J van Wijnen;Janet L Stein;Martin Montecino;Amjad Javed;Sayyed K Zaidi;Daniel W Young;Je-Yong Choi;Shirwin M Pockwinse - 通讯作者:
Shirwin M Pockwinse
Janet L Stein的其他文献
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{{ truncateString('Janet L Stein', 18)}}的其他基金
Experimental Integration, Design and Analysis Core
实验集成、设计和分析核心
- 批准号:
10608063 - 财政年份:2021
- 资助金额:
$ 3.94万 - 项目类别:
Experimental Integration, Design and Analysis Core
实验集成、设计和分析核心
- 批准号:
10380075 - 财政年份:2021
- 资助金额:
$ 3.94万 - 项目类别:
Chromatin Organization and Nuclear compartmentalization in Osteoblast Gene Exp...
成骨细胞基因实验中的染色质组织和核区室化...
- 批准号:
8289360 - 财政年份:2011
- 资助金额:
$ 3.94万 - 项目类别:
Chromatin Organization and Nuclear compartmentalization in Osteoblast Gene Exp...
成骨细胞基因实验中的染色质组织和核区室化...
- 批准号:
7355631 - 财政年份:2007
- 资助金额:
$ 3.94万 - 项目类别:
Runx1 Binding Sites as Scaffolds That Mediate Chromosome Translocation
Runx1 结合位点作为介导染色体易位的支架
- 批准号:
7537242 - 财政年份:2006
- 资助金额:
$ 3.94万 - 项目类别:
Runx1 Binding Sites as Scaffolds That Mediate Chromosome Translocation
Runx1 结合位点作为介导染色体易位的支架
- 批准号:
7126234 - 财政年份:2006
- 资助金额:
$ 3.94万 - 项目类别:
CHROMATIN STRUCTURE AND FUNCTION IN OSTEOBLAST GENE EXPRESSION
成骨细胞基因表达中的染色质结构和功能
- 批准号:
6448492 - 财政年份:2001
- 资助金额:
$ 3.94万 - 项目类别:
CHROMATIN STRUCTURE AND FUNCTION IN OSTEOBLAST GENE EXPRESSION
成骨细胞基因表达中的染色质结构和功能
- 批准号:
6299871 - 财政年份:2000
- 资助金额:
$ 3.94万 - 项目类别:
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