POSTTRANSLATIONAL MODIFICATIONS ON HISTONES AND HISTONE VARIANTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。多细胞生物由具有相同遗传信息但高度分化的各种细胞类型组成，每种细胞类型具有独特的基因表达模式。建立和维持这些不同的表达模式对细胞特性和生物生存至关重要，单个细胞中的异常基因表达可能导致发育异常或癌症。表观遗传调控机制利用染色质结构的动态改变，如组蛋白甲基化、乙酰化、磷酸化和泛素化，来调节基因的表达。这些翻译后修饰以组合的方式整合在一起，为细胞提供转录记忆，以在许多分裂中稳定地维持基因表达模式，并提供发育灵活性，以促进基因表达的程序性改变。利用串联质谱仪提供的前所未有的灵敏度和结构特异性，我们希望阐明哺乳动物染色质中丰富的表观遗传信息的性质和功能作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Multicellular organisms consist of various cell types with same genetic information but high degree of differentiation, characterized by a unique pattern of gene expression for each cell type. Establishment and maintenance of these diverse expression patterns is fundamentally important for cell identity and organism survival, and aberrant gene expression in a single cell can lead to developmental abnormalities or cancer. Epigenetic regulatory mechanisms employ dynamic modifications in chromatin structure, such as histone methylation, acetylation, phosphorylation and ubiquitination, to regulate gene expression. These posttranslational modifications are integrated in a combinatorial fashion to provide cells with transcriptional memory to stably maintain gene expression patterns throughout many divisions, and developmental flexibility to facilitate programmed alterations in gene expression. Equipped with the unprecedented sensitivity and structural specificity offered by tandem mass spectrometry, we are hoping to elucidate the nature and functional role of the rich epigenetic information in mammalian chromatin.