Department of Microbial Infection and Immunity and Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, Ohio, USA; email:
Annu Rev Immunol. 2022 Apr 26;40:387-411. doi: 10.1146/annurev-immunol-101320-025949. Epub 2022 Feb 4.
Cell identity and function largely rely on the programming of transcriptomes during development and differentiation. Signature gene expression programs are orchestrated by regulatory circuits consisting of acting promoters and enhancers, which respond to a plethora of cues via the action of transcription factors. In turn, transcription factors direct epigenetic modifications to revise chromatin landscapes, and drive contacts between distal promoter-enhancer combinations. In immune cells, regulatory circuits for effector genes are especially complex and flexible, utilizing distinct sets of transcription factors and enhancers, depending on the cues each cell type receives during an infection, after sensing cellular damage, or upon encountering a tumor. Here, we review major players in the coordination of gene regulatory programs within innate and adaptive immune cells, as well as integrative omics approaches that can be leveraged to decipher their underlying circuitry.
细胞的身份和功能在很大程度上依赖于其在发育和分化过程中转录组的编程。特征基因表达程序由包含作用启动子和增强子的调控回路来调控,这些调控回路通过转录因子的作用对大量信号做出响应。反过来,转录因子指导表观遗传修饰来修改染色质景观,并驱动远端启动子-增强子组合之间的接触。在免疫细胞中,效应基因的调控回路尤其复杂和灵活,根据每种细胞类型在感染、感知细胞损伤或遇到肿瘤时接收到的信号,利用不同的转录因子和增强子。在这里,我们回顾了先天和适应性免疫细胞中基因调控程序协调的主要参与者,以及可以用来破译其潜在回路的整合组学方法。