RT Journal Article
SR Electronic
T1 Multiplex-GAM: genome-wide identification of chromatin contacts yields insights not captured by Hi-C
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.31.230284
DO 10.1101/2020.07.31.230284
A1 Robert A. Beagrie
A1 Christoph J. Thieme
A1 Carlo Annunziatella
A1 Catherine Baugher
A1 Yingnan Zhang
A1 Markus Schueler
A1 Alexander Kukalev
A1 Rieke Kempfer
A1 Andrea M. Chiariello
A1 Simona Bianco
A1 Yichao Li
A1 Antonio Scialdone
A1 Lonnie R. Welch
A1 Mario Nicodemi
A1 Ana Pombo
YR 2021
UL http://biorxiv.org/content/early/2021/03/08/2020.07.31.230284.abstract
AB Technologies for measuring 3D genome topology are increasingly important for studying mechanisms of 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 to map chromatin contacts genome-wide. We perform a detailed comparison of contacts obtained by multiplex-GAM and Hi-C using mouse embryonic stem (mES) cells. We find that both methods detect similar topologically associating domains (TADs). However, 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 currently go under-estimated in genome-wide ligation-based approaches, and highlights the need for orthogonal advances in genome-wide contact mapping technologies.Competing Interest StatementA.P., M.N., R.A.B., A.S. hold a patent on 'Genome Architecture Mapping': Pombo, A., Edwards, P. A. W., Nicodemi, M., Beagrie, R. A. & Scialdone, A. Patent PCT/EP2015/079413 (2015).