Department of Environmental and Public Health Sciences, Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Toxicol Sci. 2021 Jul 16;182(1):1-9. doi: 10.1093/toxsci/kfab050.
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor well-known for its adaptive role as a sensor of environmental toxicants and mediator of the metabolic detoxification of xenobiotic ligands. In addition, a growing body of experimental data has provided indisputable evidence that the AHR regulates critical functions of cell physiology and embryonic development. Recent studies have shown that the naïve AHR-that is, unliganded to xenobiotics but activated endogenously-has a crucial role in maintenance of embryonic stem cell pluripotency, tissue repair, and regulation of cancer stem cell stemness. Depending on the cellular context, AHR silences the expression of pluripotency genes Oct4 and Nanog and potentiates differentiation, whereas curtailing cellular plasticity and stemness. In these processes, AHR-mediated contextual responses and outcomes are dictated by changes of interacting partners in signaling pathways, gene networks, and cell-type-specific genomic structures. In this review, we focus on AHR-mediated changes of genomic architecture as an emerging mechanism for the AHR to regulate gene expression at the transcriptional level. Collective evidence places this receptor as a physiological hub connecting multiple biological processes whose disruption impacts on embryonic development, tissue repair, and maintenance or loss of stemness.
芳香烃受体（AHR）是一种配体激活的转录因子，以作为环境毒物的传感器和外源性配体代谢解毒的介质的适应性作用而闻名。此外，越来越多的实验数据提供了无可争议的证据，表明 AHR 调节细胞生理学和胚胎发育的关键功能。最近的研究表明，原始 AHR（即未与外源性配体结合但内源性激活的 AHR）在维持胚胎干细胞多能性、组织修复和调节癌症干细胞干性方面起着至关重要的作用。根据细胞环境的不同，AHR 沉默多能性基因 Oct4 和 Nanog 的表达并促进分化，而抑制细胞可塑性和干性。在这些过程中，AHR 介导的信号通路、基因网络和细胞类型特异性基因组结构中的相互作用伙伴的变化决定了上下文反应和结果。在这篇综述中，我们专注于 AHR 介导的基因组结构变化，作为 AHR 在转录水平上调节基因表达的一种新兴机制。综合证据表明，该受体是一个生理枢纽，连接着多个生物学过程，其破坏会影响胚胎发育、组织修复以及干性的维持或丧失。
