Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology (BIMSB), Epigenetic Regulation and Chromatin Architecture Group, Berlin, Germany.
Laboratory of Gene Regulation, Weatherall Institute of Molecular Medicine, Oxford, UK.
Nat Methods. 2023 Jul;20(7):1037-1047. doi: 10.1038/s41592-023-01903-1. Epub 2023 Jun 19.
Technology for measuring 3D genome topology is increasingly important for studying gene regulation, for genome assembly and for mapping of genome rearrangements. Hi-C and other ligation-based methods have become routine but have specific biases. Here, we develop multiplex-GAM, a faster and more affordable version of genome architecture mapping (GAM), a ligation-free technique that maps chromatin contacts genome-wide. We perform a detailed comparison of multiplex-GAM and Hi-C using mouse embryonic stem cells. When examining the strongest contacts detected by either method, we find that only one-third of these are shared. The strongest contacts specifically found in GAM often involve 'active' regions, including many transcribed genes and super-enhancers, whereas in Hi-C they more often contain 'inactive' regions. Our work shows that active genomic regions are involved in extensive complex contacts that are currently underestimated in ligation-based approaches, and highlights the need for orthogonal advances in genome-wide contact mapping technologies.
用于测量 3D 基因组拓扑结构的技术对于研究基因调控、基因组组装和基因组重排作图越来越重要。Hi-C 和其他基于连接的方法已经成为常规方法，但具有特定的偏差。在这里，我们开发了 multiplex-GAM，这是一种更快、更经济的基因组结构图谱（GAM）技术，这是一种无需连接的技术，可以全基因组图谱染色质接触。我们使用小鼠胚胎干细胞对 multiplex-GAM 和 Hi-C 进行了详细比较。当检查这两种方法检测到的最强接触时，我们发现只有三分之一是共享的。在 GAM 中专门发现的最强接触通常涉及“活跃”区域，包括许多转录基因和超级增强子，而在 Hi-C 中，它们更经常包含“不活跃”区域。我们的工作表明，活跃的基因组区域参与了广泛的复杂接触，而这些接触在基于连接的方法中目前被低估了，这凸显了在全基因组接触图谱技术方面需要正交进展的必要性。
