Gao Cong, Glass Karen C, Frietze Seth
Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT, United States.
Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT, United States.
Front Bioinform. 2022 Aug 10;2:835892. doi: 10.3389/fbinf.2022.835892. eCollection 2022.
Bromodomains are a structurally conserved epigenetic reader domain that bind to acetylated lysine residues in both histone and non-histone proteins. Bromodomain-containing proteins (BRD proteins) often function as scaffolding proteins in the assembly of multi-protein complexes to regulate diverse biological processes. BRD proteins have been classified based on biological and functional similarity, however the functions of many BRD proteins remains unknown. PPI network analysis is useful for revealing organizational roles, identifying functional clusters, and predicting function for BRD proteins. We used available data to construct protein-protein interaction networks (PPINs) to study the properties of the human bromodomain protein family. The network properties of the BRD PPIN establishes that the BRD proteins serve as hub proteins that are enriched near the global center to form an inter-connected PPIN. We identified dense subgraphs formed by BRD proteins and find that different BRD proteins share topological similarity and functional associations. We explored the functional relationships through clustering and Hallmark pathway gene set enrichment analysis and identify potential biological roles for different BRD proteins. In our network analysis we confirmed that BRD proteins are conserved central nodes in the human PPI network and function as scaffolds to form distinctive functional clusters. Overall, this study provides detailed insight into the predictive functions of BRD proteins in the context of functional complexes and biological pathways.
溴结构域是一种结构保守的表观遗传读取结构域，可与组蛋白和非组蛋白中的乙酰化赖氨酸残基结合。含溴结构域的蛋白质（BRD蛋白）在多蛋白复合物的组装中常作为支架蛋白发挥作用，以调节多种生物学过程。BRD蛋白已根据生物学和功能相似性进行了分类，然而许多BRD蛋白的功能仍不清楚。蛋白质-蛋白质相互作用（PPI）网络分析有助于揭示组织作用、识别功能簇并预测BRD蛋白的功能。我们利用现有数据构建蛋白质-蛋白质相互作用网络（PPINs）来研究人类溴结构域蛋白家族的特性。BRD PPIN的网络特性表明，BRD蛋白作为枢纽蛋白富集在全局中心附近，形成一个相互连接的PPIN。我们鉴定了由BRD蛋白形成的密集子图，发现不同的BRD蛋白具有拓扑相似性和功能关联。我们通过聚类和特征通路基因集富集分析探索了功能关系，并确定了不同BRD蛋白的潜在生物学作用。在我们的网络分析中，我们证实BRD蛋白是人类PPI网络中保守的中心节点，并作为支架形成独特的功能簇。总体而言，本研究在功能复合物和生物学途径的背景下，对BRD蛋白的预测功能提供了详细的见解。
