Global Analysis of Chromatin during Lineage Development

描述（由申请人提供）：最近，微阵列技术已被用于测量基因组全转录模式，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。大规模的基因敲低实验现在也可以用于分析多动物细胞中的基因功能。多能间充质细胞可以无限繁殖，并在数周内分化为许多不同细胞系中的任何一种，其方式由培养条件控制。除了序列特异性的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进行修饰。进一步的蛋白质组已被确定为遗传和生物化学功能稳定基因活性或沉默，与染色质修饰相互作用或参与。快速接受任何细胞系承诺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，可以从根本上认识多潜能和谱系选择的机制，并有可能指导再生医学的实验发展。

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.