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（由申请人提供）：最近已经实施了微阵列Technoloy用于测量，例如基因组宽的转录模式，并且使用基因组片段阵列进行了镀铬免疫沉淀分析，这对于哺乳动物细胞是可行的。 现在，也可以实现大规模基因敲低实验，以分析来自多叶酸盐细胞中的基因功能。已经鉴定出可以在数周内以培养条件控制的方式在数周内无限期地分化为多个不同细胞谱系中的任何一个，可以无限期地分化为几周内的任何一个。除了序列特异性DNA结合蛋白外，基因表达还可以通过DNA甲基化状态以及核小体核心组蛋白中修饰残基的类型和位置来改变基因表达。在遗传和生化上已经鉴定出进一步的蛋白质组，以稳定基因活性或静音，并与或参与染色质修饰。快速承诺对许多细胞谱系中的任何一个中的任何一种的能力都可以耦合到维持基因激活或沉默或沉默或有效功能的机制的限制，以逆转基因的沉默和激活状态。新一代基因组技术的应用可以使人们对多能性和谱系选择的机制以及对再生医学开发的潜在指南实验的基本见解。