Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.
Front Immunol. 2021 May 14;12:669881. doi: 10.3389/fimmu.2021.669881. eCollection 2021.
Proper lymphopoiesis and immune responses depend on the spatiotemporal control of multiple processes, including gene expression, DNA recombination and cell fate decisions. High-order 3D chromatin organization is increasingly appreciated as an important regulator of these processes and dysregulation of genomic architecture has been linked to various immune disorders, including lymphoid malignancies. In this review, we present the general principles of the 3D chromatin topology and its dynamic reorganization during various steps of B and T lymphocyte development and activation. We also discuss functional interconnections between architectural, epigenetic and transcriptional changes and introduce major key players of genomic organization in B/T lymphocytes. Finally, we present how alterations in architectural factors and/or 3D genome organization are linked to dysregulation of the lymphopoietic transcriptional program and ultimately to hematological malignancies.
适当的淋巴发生和免疫反应取决于多个过程的时空控制,包括基因表达、DNA 重组和细胞命运决定。越来越多的人认为高阶 3D 染色质组织是这些过程的重要调节剂,基因组结构的失调与各种免疫紊乱有关,包括淋巴恶性肿瘤。在这篇综述中,我们介绍了 3D 染色质拓扑结构的一般原理及其在 B 和 T 淋巴细胞发育和激活的各个步骤中的动态重排。我们还讨论了结构、表观遗传和转录变化之间的功能联系,并介绍了 B/T 淋巴细胞中基因组组织的主要关键因子。最后,我们介绍了结构因子和/或 3D 基因组组织的改变如何与淋巴发生转录程序的失调以及最终与血液恶性肿瘤有关。