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: 7881180
• 负责人: SHERMAN Morton WEISSMAN
• 金额: $ 4.81万
• 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/7881180
• 关键词: Acetylation; Biological Assay; Cell Line; Cell Lineage; Cells; Chromatin; Complementary DNA; Computer Systems Development; 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; Oligonucleotide Microarrays; Oligonucleotides; Pattern; Positioning Attribute; Procedures; Promoter Regions; Proteins; RNA Interference; Regenerative Medicine; Role; Sequence-Specific DNA Binding Protein; Surveys; System; Techniques; Time; Undifferentiated; cell type; chromatin immunoprecipitation; chromatin modification; cost; embryonic stem cell; gene function; genome-wide; histone modification; insight; monocyte; neutrophil; precursor cell; promoter; research study; stem cell differentiation

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（由申请人提供）：最近，微阵列技术已被用于测量，例如全基因组转录模式，并且使用基因组片段阵列的染色免疫沉淀分析已被证明对哺乳动物细胞是可行的。 大规模的基因敲除实验现在也可以用于分析来自多动物的细胞中的基因功能。多能间充质细胞已被鉴定为可以无限繁殖并在数周内分化成许多不同细胞谱系中的任一种，其方式受培养条件控制。除了序列特异性DNA结合蛋白之外，基因表达还可以通过DNA甲基化的状态以及核小体核心组蛋白中修饰残基的类型和位置来修饰。已经从遗传学和生物化学上鉴定了其他蛋白质组，其功能是稳定基因活性或沉默，并与染色质修饰相互作用或参与染色质修饰。快速定型为任何细胞谱系的能力可能与维持基因激活或沉默的机制的限制或逆转基因沉默和激活状态的机制的有效功能有关。新一代基因组技术的应用可以为多潜能性和谱系选择的机制提供基本的见解，并有可能指导再生医学的发展。