ABSTRACT

The hierarchical three-dimensional folding of the mammalian genome constitutes an important regulatory layer of gene expression and cell fate control during processes such as development and tumorigenesis. Accumulating evidence supports the existence of complex topological assemblies in which multiple genes and regulatory elements are frequently interacting with each other in the 3D nucleus. Here, we will discuss the nature, organizational principles, and potential function of such assemblies, including the recently reported enhancer “hubs,” “cliques,” and FIREs (frequently interacting regions) as well as multi-contact hubs. We will also review recent studies that investigate the role of transcription factors (TFs) in driving the topological genome reorganization and hub formation in the context of cell fate transitions and cancer. Finally, we will highlight technological advances that enabled these studies, current limitations, and future directions necessary to advance our understating in the field.

摘要

哺乳动物基因组的分层三维折叠构成了在发育和肿瘤发生等过程中基因表达和细胞命运控制的重要调控层。越来越多的证据支持复杂拓扑组件的存在，其中多个基因和调控元件在 3D 细胞核中经常相互作用。在这里，我们将讨论此类程序集的性质、组织原则和潜在功能，包括最近报道的增强子“枢纽”、“派系”和 FIRE（频繁交互区域）以及多接触枢纽。我们还将回顾最近的研究，这些研究调查了转录因子 (TF) 在细胞命运转变和癌症背景下在驱动拓扑基因组重组和中心形成方面的作用。最后，