The second decade of 3C technologies: detailed insights into nuclear organization.
The second decade of 3C technologies: detailed insights into nuclear organization.
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DOI：
10.1101/gad.281964.116
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发表时间：
2016-06-15
影响因子：
10.5
通讯作者：
de Laat W
中科院分区：
文献类型：
--
作者：
Denker A;de Laat W
Denker和de Laat描述了不同3C方法之间的差异和共性，并解释了对3D基因组的更详细的见解如何有助于理解发育中的转录调控和疾病中的放松调控。三维（3D）基因组组织的相关性，转录调控，从而细胞的命运，现在被广泛接受。我们对这一功能背后的迷人架构的理解是基于显微镜研究以及染色体构象捕获（3C）方法，该方法在千禧年开始时进入了这个阶段。3C方法的第一个十年为基因组拓扑结构提供了前所未有的见解。在这里，我们提供了最近几年的发展和发现的最新情况。正如我们所讨论的，建立和新开发的实验和计算方法，使识别新的，功能重要的染色体结构。整个基因组中的调控和结构染色质环正在被编目，并在细胞类型之间进行比较，揭示组织不变和发育动态环。塑造基因组的结构蛋白质被揭示出来，它们的作用模式也正在被揭示出来。我们解释了如何更详细的见解3D基因组增加我们的理解转录调控的发展和疾病的失调。最后，为了帮助研究人员选择最适合其特定研究问题的方法，我们解释了各种3C衍生方法之间的差异和共性。
Denker and de Laat describe differences and commonalities between the different 3C methods and explain how more detailed insights into the 3D genome aid in understanding transcriptional regulation in development and deregulation in disease. The relevance of three-dimensional (3D) genome organization for transcriptional regulation and thereby for cellular fate at large is now widely accepted. Our understanding of the fascinating architecture underlying this function is based on microscopy studies as well as the chromosome conformation capture (3C) methods, which entered the stage at the beginning of the millennium. The first decade of 3C methods rendered unprecedented insights into genome topology. Here, we provide an update of developments and discoveries made over the more recent years. As we discuss, established and newly developed experimental and computational methods enabled identification of novel, functionally important chromosome structures. Regulatory and architectural chromatin loops throughout the genome are being cataloged and compared between cell types, revealing tissue invariant and developmentally dynamic loops. Architectural proteins shaping the genome were disclosed, and their mode of action is being uncovered. We explain how more detailed insights into the 3D genome increase our understanding of transcriptional regulation in development and misregulation in disease. Finally, to help researchers in choosing the approach best tailored for their specific research question, we explain the differences and commonalities between the various 3C-derived methods.