Molecular Barcodes Involved in Epigenetic Reprogramming

描述（由申请人提供）：胚胎干细胞在分化为特定细胞类型期间经历大量变化。这些变化必须延伸到这些细胞基因组的重组，如果不是起源于这些细胞基因组的重组，这很可能涉及遗传和表观遗传（不在DNA序列中编码）因素。表观遗传修饰系统控制细胞/生物体发育期间或可能也在疾病状态期间基因表达的稳定性。这些表观遗传调节因子之一是染色质相关蛋白如组蛋白和高迁移率族（HMG）蛋白的翻译后修饰。这些修饰已被证明可以调节多种生物学事件，如基因激活、基因沉默或在DNA修复机制中发挥作用。使用高端质谱，将以定性和定量的方式对来自干细胞和分化细胞的组蛋白和HMG蛋白的修饰状态进行深入研究。这项研究提案为理解可能参与细胞分化的表观遗传机制提供了一个坚实的开端，并可能产生重要的信息，从而改善干细胞技术的治疗应用。

DESCRIPTION (provided by applicant): Embryonic stem cells go through large amounts of changes during differentiation into specific cell types. The changes must extend to, if not origin from reorganization of the genomes of these cells, which would most likely involve genetic and epigenetic (not encoded for in DNA sequence) factors. Epigenetic modification systems control stability of gene expression during cell/organism development or possibly also during diseased states. One of these epigenetic regulators is the post-translational modification of chromatin- associated proteins such as histones and high-mobility group (HMG) proteins. These modifications have been shown to modulate a variety of biological events such as gene activation, gene silencing or have roles in DNA repair mechanisms. Using high end mass spectrometry, an in-depth investigation of the modification states of histones and HMG proteins from stem and differentiated cells will be performed in both a qualitative and quantitative manner. This research proposal provides a solid start in understanding the epigenetic mechanisms that may be involved in cellular differentiation and could yield significant information that could lead to improved stem cell technology for therapeutic applications.