Global Analysis of Chromatin during Lineage Development

谱系发育过程中染色质的整体分析

基本信息

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
项目类别：
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

项目摘要

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于哺乳动物细胞是可行的。现在还可以进行大规模基因敲除实验，以分析多动物细胞中的基因功能。多能间充质细胞已被鉴定为可以无限繁殖并在数周内以培养条件控制的方式分化成多种不同细胞谱系中的任何一种。除了序列特异性 DNA 结合蛋白之外，基因表达还可以通过 DNA 甲基化状态以及核小体核心组蛋白中修饰残基的类型和位置进行修饰。进一步的蛋白质组已在遗传学和生物化学上被鉴定出，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。快速定型为多种细胞谱系中的任何一种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和谱系选择的机制提供基础见解，并为再生医学的发展提供潜在的指导实验。