CHARACTERIZATION OF HUMAN HISTONES WITH COMPLEX PTMS BY ECD

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 虽然核心组蛋白是细胞中最保守的蛋白质之一，但它们在整个序列中具有广泛的甲基化、乙酰化、磷酸化和泛素化以及特定的额外关键修饰。在不同残基位置处的不同数目的PTM的各种组合允许细胞产生许多不同的PTM配置以及响应于细胞线索动态地改变特定位点。有人提出，这些配置与表观遗传调控。然而，核心组蛋白及其PTM构型的详细表征迄今为止是一项艰巨的任务。分析大量修饰的组蛋白的困难来自于这样的事实，即由于PTM的组合性质，可能存在许多，有时数千种可能的PTM构型，占据不同的位点。 在这个项目中，我们打算开发新的技术来解决一些最具挑战性的问题，在质谱为基础的蛋白质组学领域。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Although core histones are among the most conserved proteins in the cell, they bear an extensive population of methylations, acetylations, phosphorylations, and ubiquitination as well as particular additional key modifications throughout their sequences. The various combinations of different numbers of PTMs at different residue locations allow the cell to generate many different PTM configurations as well as alter particular sites dynamically in response to cellular cues. It has been proposed that those configurations are associated with epigenetic regulations. However, detailed characterization of core histones and their PTM configurations is thus far a difficult task. The difficulty for analysis of heavily modified histones arises from the fact that many, sometimes thousands of possible PTM configurations may exist due to the combinatorial nature of PTMs, occupying different sites. In this project, we intend to develop novel technologies to solve some of the most challenging problems in the mass spectrometry based proteomics filed.