激素依赖性癌症中的长程基因调控
SCI
12 August 2023
Long-range gene regulation in hormone-dependent cancer
（nature reviews cancer, IF: 78.5）
Theophilus T. Tettey, Lorenzo Rinaldi & Gordon L. Hager
CORRESPONDENCE TO: hagerg@exchange.nih.gov
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.
人类基因组由多个结构层组成，从染色体区域到更小的亚结构，如拓扑关联域（TAD）和染色质环。这些亚结构统称为长程染色质相互作用（LRIs），在调控基因表达方面发挥着重要作用。TADs是基因组中包含基因组和调控元件的区域，这些基因组和调控元件经常相互影响，并与其他区域隔离，从而防止了DNA的广泛失控接触。通过增强子和启动子相互作用在 TADs 内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，三维基因组结构也称为染色质结构显然是许多转录细胞决定的核心。在本综述中，我们将深入探讨类固醇受体与 LRIs 之间错综复杂的关系，讨论类固醇受体如何与这些染色质相互作用并对其进行调节。涉及核结构组织的许多过程的基因改变往往与激素依赖性癌症的发生有关。更好地了解核结构蛋白与激素调控网络之间的相互作用，最终可以开发出更好的癌症治疗方法。
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