Multiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C

Journal article

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

Authors: Beagrie, RA; Thieme, CJ; Annunziatella, C; Baugher, C; Zhang, Y

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Methods
• Volume: 20
• Issue: 7
• Pages: 1037-1047
• Publication date: 2023-06-19
• DOI: 10.1038/s41592-023-01903-1
• EISSN: 1548-7105
• ISSN: 1548-7091
• Language: English
• Keywords: Chromosome conformation capture; Genome; ChIA-PET; Enhancer; Biology; Genetics; Chromatin; Multiplex; Chromatin remodeling; Gene; Gene expression; Computational biology