Multilevel Proteomics Reveals Epigenetic Signatures in BCG-Mediated Macrophage Activation.

IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Zoe Schaefer, John Iradukunda, Evelyn N Lumngwena, Kari B Basso, Jonathan M Blackburn, Ivana K Parker
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Abstract

The bacillus Calmette-Guérin BCG vaccine (Mycobacterium bovis) is primarily used to prevent tuberculosis (TB) infections but has wide-ranging immunogenic effects. One of its most notable properties is its ability to induce trained immunity, a memory-like response in innate immune cells such as macrophages. Through targeted analyses of well-established histone marks, prior research has shown that these changes are generated through epigenetic modification. Mass spectrometry-based proteomic approaches provide a way to globally profile various aspects of the proteome, providing data to further identify unexplored mechanisms of BCG-mediated immunomodulation. Here we use multi-level proteomics (total, histone, and phospho to identify networks and potential mechanisms that mediate BCG-induced immunomodulation in macrophages. Histone-focused proteomics and total proteomics were performed at the University of Cape Town (data available via ProteomeXchange with identifier PXD051187), while phosphoproteomics data was retrieved from the ProteomeXchange Repository (identifier PXD013171). We identify several epigenetic mechanisms that may drive BCG-induced training phenotypes. Evidence across the proteomics and histone-focused proteomics data set pair 6 epigenetic effectors (NuA4, NuRD, NSL, Sin3A, SIRT2, SIRT6) and their substrates.

多层次蛋白质组学揭示卡介苗介导的巨噬细胞活化过程中的表观遗传学特征
卡介苗(牛分枝杆菌)主要用于预防结核病(TB)感染,但具有广泛的免疫原性。卡介苗最显著的特性之一是能够诱导训练免疫,即巨噬细胞等先天性免疫细胞的记忆反应。通过对已确立的组蛋白标记进行有针对性的分析,先前的研究表明这些变化是通过表观遗传修饰产生的。基于质谱的蛋白质组学方法提供了一种全面剖析蛋白质组各个方面的方法,为进一步确定卡介苗介导的免疫调节的未探索机制提供了数据。在这里,我们使用多级蛋白质组学(总蛋白、组蛋白和磷酸化蛋白)来确定介导卡介苗诱导巨噬细胞免疫调节的网络和潜在机制。组蛋白组学和总蛋白质组学是在开普敦大学进行的(数据可通过 ProteomeXchange 获取,标识符为 PXD051187),而磷酸化蛋白质组学数据则是从 ProteomeXchange 存储库(标识符为 PXD013171)获取的。我们发现了几种可能驱动卡介苗诱导的训练表型的表观遗传学机制。蛋白质组学和以组蛋白为重点的蛋白质组学数据集中的证据对6种表观遗传效应因子(NuA4、NuRD、NSL、Sin3A、SIRT2、SIRT6)及其底物进行了配对。
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来源期刊
Molecular & Cellular Proteomics
Molecular & Cellular Proteomics 生物-生化研究方法
CiteScore
11.50
自引率
4.30%
发文量
131
审稿时长
84 days
期刊介绍: The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes
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