POSTTRANSLATIONAL MODIFICATIONS ON HISTONES AND HISTONE VARIANTS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。多细胞生物体由具有相同遗传信息但高度分化的各种细胞类型组成，其特征在于每种细胞类型的基因表达模式独特。这些不同表达模式的建立和维持对于细胞身份和生物体存活至关重要，并且单个细胞中的异常基因表达可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修饰，如组蛋白甲基化、乙酰化、磷酸化和泛素化，来调控基因表达。这些翻译后修饰以组合方式整合，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。配备了前所未有的灵敏度和结构特异性提供串联质谱，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.