由DNA围绕核心组蛋白所形成的核小体，经过高度折叠形成染色质结构，而染色质结构的改变对基因的转录调控以及细胞内的多种生物过程起着至关重要的作用。目前认为，染色质结构的改变主要由具有酶活性的多亚基复合物通过组蛋白的翻译后修饰、染色质重塑以及组蛋白变体与标准组蛋白间的置换等来实现。已有研究表明，组蛋白变体H2AZ的置换在基因转录调控以及DNA损伤修复等过程中都起着重要的作用。最近，我们利用体外H2AZ置换酶活性检测系统，通过对人细胞核提取物经过多步骤分离纯化的方法，对其蛋白组分进行跟踪检测，发现了具有催化H2AZ-H2A间置换的蛋白酶活性组分，多维蛋白质谱分析结果表明，此酶活性与已发表的SRCAP酶复合物无关，提示可能为一种新的人组蛋白变体H2AZ置换酶。在本项目研究中，将进一步纯化与鉴定这一新的人组蛋白变体H2AZ置换酶的亚基分子组分，并阐明其在细胞内的生物学功能以及其作用机理。

Highly folded chromatin structure is packaged by chromosomal DNA wrapped around histone octamers composed of two copies of each canonical histone H3, H4, H2A and H4. Alterations in chromatin structure play a key role in gene transcription regulation and a variety of biological processes in cells. It has been known that changes in chromatin structure are regulated in at least three different ways: by post-translational modifications of histones, by ATP-dependent remodeling of nucleosomes, and by the deposition/eviction of histone variants. Previous studies have shown that deposition/eviction of histone variant H2AZ is involved in many biological processes in cells including gene transcription regulation, chromosome segregation, and DNA damage repair. Recently, by tracking and detecting the protein fractions which has been purified from HeLa cell nuclear extracts through multi-step chromatography using in vitro H2AZ deposition enzyme activity assay system, we found the catalytic protein fractions which can catalyze the exchange between histone variant H2AZ and canonical histone H2A. Multidimensional Protein Identification (MudPIT) analysis indicated that the catalytic protein fractions are unrelated with the SRCAP complex which is published previously, suggesting a novel human histone variant H2AZ replacement enzyme. In this project, we will further identify and characterize this novel H2AZ replacement enzyme and its subunit composition, and we will also clarify its biological functions in the cells and its action mechanisms.