CHARACTERIZATION OF HUMAN HISTONES WITH COMPLEX PTMS BY ECD

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级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，但它们在其整个序列中承载着广泛的甲基化、乙酰化、磷酸化和泛素化以及特殊的额外关键修饰。不同残基位置的不同数量的PTM的各种组合允许细胞产生许多不同的PTM配置，以及响应于细胞提示动态地改变特定的位置。有人提出，这些构型与表观遗传调控有关。然而，到目前为止，对核心组蛋白及其PTM构型的详细表征是一项艰巨的任务。分析大量修饰的组蛋白的困难源于这样一个事实，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，占据不同的位置。在这个项目中，我们打算开发新的技术来解决基于质谱学的蛋白质组学领域中一些最具挑战性的问题。

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.