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


  • R.A. Beagrie
  • C.J. Thieme
  • C. Annunziatella
  • C. Baugher
  • Y. Zhang
  • M. Schueler
  • A. Kukalev
  • R. Kempfer
  • A.M. Chiariello
  • S. Bianco
  • Y. Li
  • T. Davis
  • A. Scialdone
  • L.R. Welch
  • M. Nicodemi
  • A. Pombo


  • Nature Methods


  • Nat Methods 20 (7): 1037-1047


  • 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.