Global Analysis of Chromatin during Lineage Development

谱系发育过程中染色质的整体分析

• 批准号: 7455839
• 负责人: SHERMAN Morton WEISSMAN
• 金额: $ 58.93万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7455839
• 关键词: Acetylation; Biological Assay; Cell Differentiation process; Cell Line; Cell Lineage; Cells; Chromatin; Complementary DNA; Computer Systems Development; Condition; Conserved Sequence; Coupled; CpG Islands; DNA; DNA Methylation; DNA Modification Process; Data; Development; Erythroid; Event; Gene Activation; Gene Expression; Generations; Genes; Genetic Transcription; Genome; Genomics; Hematopoietic; Hematopoietic stem cells; Histones; Homeodomain Proteins; Human; Immunoprecipitation; In Vitro; Individual; Lymphoid; Lysine; Maintenance; Mammalian Cell; Measurement; Mesenchymal; Messenger RNA; Methylation; Modification; Molecular; Mus; Nucleosomes; Numbers; Oligonucleotide Microarrays; Oligonucleotides; Pattern; Polymerase Chain Reaction; Positioning Attribute; Procedures; Promoter Regions; Proteins; RNA Interference; Regenerative Medicine; Role; Sequence-Specific DNA Binding Protein; Surveys; System; Techniques; Time; Undifferentiated; Week; cell type; chromatin immunoprecipitation; cost; embryonic stem cell; gene function; insight; monocyte; neutrophil; precursor cell; promoter; research study

DESCRIPTION (provided by applicant): Recently microarray technoloy has been implemented for measurements such as genome wide transcription patterns, and chromation immunoprecipitation analysis using genomic fragment arrays has been shown to be feasible for mammalian cells. Large scale gene knockdown experiments are also now achievable for analysis of gene function in cells from multizoates. Multipotential mesenchymal cells have been identified that can be propagated indefinitely amd differentiate within weeks into any one of a number of different cell lineages, in a manner controlled by the culture conditions. In addition to sequence specific DNA binding proteins, gene expression can be modified by the state of DNA methylation and the types and positions of modified residues in the core histones of nucleosomes. Further groups of proteins have been identified genetically and biochemically that function to stabilize gene activity or silence and interact with or participate in chromatin modification. The ability to rapidly undergo commitment to any of a number of cell lineages may be coupled to either limitations in the mechanisms for maintenance of gene activation or silencing or efficient functioning of mechanisms to reverse silenced and activated states of genes. Application of the new generation of genomic techniques could give fundamental insight into the mechanisms of multipotentiality and lineage choice and potential guide experimentation towards the development of regenerative medicine.

描述(申请人提供)：最近，微阵列技术已被用于诸如全基因组转录模式的测量，使用基因组片段阵列的显色免疫沉淀分析已被证明对哺乳动物细胞是可行的。现在还可以进行大规模的基因敲除实验，以分析多栖动物细胞中的基因功能。已经鉴定出多潜能间充质细胞可以无限繁殖，并在几周内以受培养条件控制的方式分化为多种不同细胞系中的任何一种。除了序列特异的DNA结合蛋白外，DNA甲基化状态和修饰残基在核小体核心组蛋白中的类型和位置也可以改变基因的表达。进一步的蛋白质组已经被基因和生化鉴定，它们的功能是稳定基因活性或沉默以及与染色质修饰相互作用或参与染色质修饰。能够迅速接受对多种细胞系中任何一种的承诺可能与维持基因激活或沉默的机制的局限性或逆转基因沉默和激活状态的机制的有效运作有关。新一代基因组技术的应用可以从根本上揭示多潜能和谱系选择的机制，并有可能指导实验向再生医学的发展。