文章：

激素依赖性癌症的远程基因调控

Long-range gene regulation in hormone-dependent cancer

原文发布日期：2023-08-03

DOI: 10.1038/s41568-023-00603-4

类型: Review Article

开放获取: 否

英文摘要：

The human genome is organized into multiple structural layers, ranging from chromosome territories to progressively smaller substructures, such as topologically associating domains (TADs) and chromatin loops. These substructures, collectively referred to as long-range chromatin interactions (LRIs), have a significant role in regulating gene expression. TADs are regions of the genome that harbour groups of genes and regulatory elements that frequently interact with each other and are insulated from other regions, thereby preventing widespread uncontrolled DNA contacts. Chromatin loops formed within TADs through enhancer and promoter interactions are elastic, allowing transcriptional heterogeneity and stochasticity. Over the past decade, it has become evident that the 3D genome structure, also referred to as the chromatin architecture, is central to many transcriptional cellular decisions. In this Review, we delve into the intricate relationship between steroid receptors and LRIs, discussing how steroid receptors interact with and modulate these chromatin interactions. Genetic alterations in the many processes involved in organizing the nuclear architecture are often associated with the development of hormone-dependent cancers. A better understanding of the interplay between architectural proteins and hormone regulatory networks can ultimately be exploited to develop improved approaches for cancer treatment.

摘要翻译： 

人类基因组被组织成多个结构层次，从染色体领域到逐渐更小的亚结构，如拓扑关联结构域（TADs）和染色质环。这些亚结构统称为长程染色质相互作用（LRIs），在调控基因表达中发挥重要作用。TADs是基因组中的区域，包含成簇的基因和调控元件，这些基因和元件之间频繁相互作用，并与其他区域隔离，从而防止不受控制的DNA广泛接触。TADs内通过增强子和启动子相互作用形成的染色质环具有弹性，允许转录异质性和随机性。在过去十年中，3D基因组结构（也称为染色质结构）在许多转录细胞决策中的核心作用日益凸显。在本综述中，我们深入探讨类固醇受体与LRIs之间的复杂关系，讨论类固醇受体如何与这些染色质相互作用并调节它们。在组织核结构的众多过程中，遗传改变常与激素依赖性癌症的发生相关。更深入地理解结构蛋白与激素调控网络之间的相互作用，最终可被用于开发更优的癌症治疗方法。

原文链接：

Long-range gene regulation in hormone-dependent cancer