心脏发育和疾病中的三维染色质组织。
Three-dimensional chromatin organization in cardiac development and disease.
机构信息
Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA.
Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, 650 Charles Young Dr, Los Angeles, CA 90095, USA.
出版信息
J Mol Cell Cardiol. 2021 Feb;151:89-105. doi: 10.1016/j.yjmcc.2020.11.008. Epub 2020 Nov 24.
Recent technological advancements in the field of chromatin biology have rewritten the textbook on nuclear organization. We now appreciate that the folding of chromatin in the three-dimensional space (i.e. its 3D "architecture") is non-random, hierarchical, and highly complex. While 3D chromatin structure is partially encoded in the primary sequence and thereby broadly conserved across cell types and states, a substantial portion of the genome seems to be dynamic during development or in disease. Moreover, there is growing evidence that at least some of the 3D structure of chromatin is functionally linked to gene regulation, both being modulated by and impacting on multiple nuclear processes (including DNA replication, transcription, and RNA splicing). In recent years, these new concepts have nourished several investigations about the functional role of 3D chromatin topology dynamics in the heart during development and disease. This review aims to provide a comprehensive overview of our current understanding in this field, and to discuss how this knowledge can inform further research as well as clinical practice.
近年来，染色质生物学领域的技术进步改写了细胞核组织的教科书。我们现在意识到，染色质在三维空间（即其 3D“结构”）中的折叠不是随机的，而是分层的，且高度复杂。虽然 3D 染色质结构部分编码在一级序列中，因此在细胞类型和状态上广泛保守，但基因组的很大一部分在发育或疾病过程中似乎是动态的。此外，越来越多的证据表明，染色质的至少一部分 3D 结构与基因调控功能相关，两者都受到多种核过程（包括 DNA 复制、转录和 RNA 剪接）的调节和影响。近年来，这些新概念催生了一些关于 3D 染色质拓扑动力学在发育和疾病过程中心脏中的功能作用的研究。本综述旨在提供该领域当前认识的全面概述，并讨论这些知识如何为进一步的研究和临床实践提供信息。
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