Gosselin David, Glass Christopher K
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Immunol Rev. 2014 Nov;262(1):96-112. doi: 10.1111/imr.12213.
Macrophages play essential roles in tissue homeostasis, pathogen elimination, and tissue repair. A defining characteristic of these cells is their ability to efficiently adapt to a variety of abruptly changing and complex environments. This ability is intrinsically linked to a capacity to quickly alter their transcriptome, and this is tightly associated with the epigenomic organization of these cells and, in particular, their enhancer repertoire. Indeed, enhancers are genomic sites that serve as platforms for the integration of signaling pathways with the mechanisms that regulate mRNA transcription. Notably, transcription is pervasive at active enhancers and enhancer RNAs (eRNAs) are tightly coupled to regulated transcription of protein-coding genes. Furthermore, given that each cell type possesses a defining enhancer repertoire, studies on enhancers provide a powerful method to study how specialization of functions among the diverse macrophage subtypes may arise. Here, we review recent studies providing insights into the distinct mechanisms that contribute to the establishment of enhancers and their role in the regulation of transcription in macrophages.
巨噬细胞在组织稳态、病原体清除和组织修复中发挥着重要作用。这些细胞的一个决定性特征是它们能够有效地适应各种突然变化的复杂环境。这种能力与快速改变其转录组的能力内在相关,并且这与这些细胞的表观基因组组织紧密相关,特别是它们的增强子库。事实上,增强子是基因组位点,作为信号通路与调节mRNA转录机制整合的平台。值得注意的是,转录在活性增强子处普遍存在,并且增强子RNA(eRNA)与蛋白质编码基因的调控转录紧密耦合。此外,鉴于每种细胞类型都拥有特定的增强子库,对增强子的研究为研究不同巨噬细胞亚型之间功能特化如何产生提供了一种强大的方法。在这里,我们综述了最近的研究,这些研究深入探讨了有助于增强子建立的不同机制及其在巨噬细胞转录调控中的作用。