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

Abstract

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  •  Schueler M  •  Kukalev A  •  Kempfer R  •  Chiariello AM  •  Bianco S  •  Li Y  •  Davis T  •  Scialdone A  •  Welch LR  •  Nicodemi M  •  Pombo A

Link

https://www.ncbi.nlm.nih.gov/pubmed/37336949