Dynamics of nucleosome positioning and the role of chromatin in myogenesis
核小体定位动力学和染色质在肌生成中的作用
基本信息
- 批准号:8448693
- 负责人:
- 金额:$ 26.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-04-06 至 2014-09-30
- 项目状态:已结题
- 来源:
- 关键词:AgingAnimal ModelAttentionBase PairingBindingCell Differentiation processCell LineCell LineageCell NucleusCellsChromatinChromatin Remodeling FactorChromatin StructureCitiesCritiquesDNADNA SequenceDNA-Binding ProteinsDataDevelopmentDevelopmental ProcessDistalDrosophila genusDrosophila melanogasterEnhancersEnzymesEventGene ExpressionGene Expression RegulationGenesGenomeGoalsGrantHematopoieticHematopoietic SystemHistonesHumanHuman GenomeK562 CellsLeadLightMapsMediator of activation proteinModelingModificationMuscle CellsNucleic Acid Regulatory SequencesNucleosomesOrganismPositioning AttributePost-Translational Protein ProcessingProcessProteinsPublished CommentRNA SequencesReadingRecruitment ActivityRegulationRegulatory ElementResearchRoleRunningStem cellsStructureSystemTechnologyTimeTranscriptTranscription CoactivatorTranscriptional RegulationWeltsWorkagedcell fate specificationchromatin remodelingclinically relevantclinically significantflygenome-widehistone modificationimprovedinsightinterestknock-downmammalian genomemultipotent cellmyogenesisprogramspromoterresearch studyresponsetranscription factor
项目摘要
The DNA of eukaryotic organisms is pacl<aged into the nucleus by wrapping around
histone proteins in a structure l<nown as chromatin. This pacl<aging can influence gene
regulation with condensed chromatin regions containing genes and their associated
regulatory elements that are inaccessible to transcriptional activators. The modulation of
chromatin structure is therefore one of the key mediators of transcriptional regulation.
The most basic unit of chromatin is the nucleosome, which consists of approximately
146 base pairs of DNA wrapped around an octamer of histone proteins. The precise
positioning of nucleosomes in functional regulatory regions of the genome can directly
influence the transcriptional regulation of nearby genes. ATP-dependent chromatin
remodeling enzymes, post-translational modifications to histones and the DNA sequence
itself have all been implicated in regulating the positioning of nucleosomes at specific
regions of the genome. We propose to investigate the roles of each of these
mechanisms in regulating the positioning of nucleosomes in the Drosophila
melanogaster and human genomes and furthermore to begin to elucidate the
relationship between chromatin and transcription factors in gene regulation. We will first
investigate the basic questions of how chromatin remodeling enzymes are recruited to
their targets and how ATP-dependent chromatin remodeling, histone modifications and
DNA sequence interact to regulate nucleosome positioning by using cultured Drosophila
cells. The insights obtained from these experiments in Drosophila cells will then be
applied to analogous experiments in human hematopoietic cells, a system for which the
network of transcription factors involved in lineage specification has been extensively
studied. By integrating data on nucleosome positioning and chromatin remodeling with
the already established transcription factor programs in these cells, I will be able to study
the interactions between chromatin and transcription factors in regulating the
transcriptional programs of cells during development. These studies will lead to a greater
understanding of the mechanisms responsible for the organization of nucleosomes
across the genome and further elucidate the role of chromatin in the regulation of
transcription.
真核生物的DNA通过缠绕进入细胞核。
现在称为染色质的结构中的组蛋白。这种衰老会影响基因
含基因及其相关基因的染色质浓缩区域的调控
转录激活剂无法访问的调控元件。信号的调制
因此,染色质结构是转录调控的关键调节因子之一。
染色质的最基本单位是核小体,它由大约
146个碱基对的DNA包裹在组蛋白的八聚体周围。精准的
核小体在基因组功能调节区的定位可以直接
影响附近基因的转录调控。依赖三磷酸腺苷的染色质
重塑酶、组蛋白的翻译后修饰和DNA序列
其本身都与调节核小体在特定区域的定位有关
基因组的区域。我们建议调查每一个人的角色
果蝇核小体定位的调控机制
和人类基因组,并进一步开始阐明
染色质与转录因子在基因调控中的关系。我们将首先
研究染色质重塑酶如何被招募到
它们的靶点以及依赖于ATP的染色质重塑、组蛋白修饰和
利用培养果蝇DNA序列相互作用调节核小体定位
细胞。从这些在果蝇细胞中的实验中获得的见解将会是
应用于人类造血细胞的类似实验,该系统
参与谱系指定的转录因子网络已被广泛研究
学习。通过将核小体定位和染色质重塑的数据与
已经在这些细胞中建立了转录因子程序,我将能够研究
染色质与转录因子在调节细胞周期中的相互作用
细胞发育过程中的转录程序。这些研究将导致更大的
对核小体组织机制的理解
并进一步阐明染色质在细胞周期调控中的作用
抄写。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
High mobility group protein N5 (HMGN5) and lamina-associated polypeptide 2α (LAP2α) interact and reciprocally affect their genome-wide chromatin organization.
高迁移率族蛋白 N5 (HMGN5) 和层相关多肽 2α (LAP2α) 相互作用并相互影响其全基因组染色质组织。
- DOI:10.1074/jbc.c113.469544
- 发表时间:2013
- 期刊:
- 影响因子:0
- 作者:Zhang,Shaofei;Schones,DustinE;Malicet,Cedric;Rochman,Mark;Zhou,Ming;Foisner,Roland;Bustin,Michael
- 通讯作者:Bustin,Michael
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Dustin Edward Schones其他文献
Dustin Edward Schones的其他文献
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{{ truncateString('Dustin Edward Schones', 18)}}的其他基金
Epigenetic dysregulation of transposons in obesity
肥胖中转座子的表观遗传失调
- 批准号:
9977151 - 财政年份:2017
- 资助金额:
$ 26.89万 - 项目类别:
Epigenetic dysregulation of transposons in obesity
肥胖中转座子的表观遗传失调
- 批准号:
9381644 - 财政年份:2017
- 资助金额:
$ 26.89万 - 项目类别:
Epigenetic dysregulation of transposons in obesity
肥胖中转座子的表观遗传失调
- 批准号:
10206119 - 财政年份:2017
- 资助金额:
$ 26.89万 - 项目类别:
Dynamics of nucleosome positioning and the role of chromatin in myogenesis
核小体定位动力学和染色质在肌生成中的作用
- 批准号:
8233771 - 财政年份:2011
- 资助金额:
$ 26.89万 - 项目类别:
Dynamics of nucleosome positioning and the role of chromatin in myogenesis
核小体定位动力学和染色质在肌生成中的作用
- 批准号:
8253686 - 财政年份:2011
- 资助金额:
$ 26.89万 - 项目类别:
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