Genome-wide absolute quantification of chromatin looping
Jusuf, J. M.; Grosse-Holz, S.; Gabriele, M.; Mach, P.; Flyamer, I. M.; Zechner, C.; Giorgetti, L.; Mirny, L.; Hansen, A. S.
Show abstract
3D genomics methods such as Hi-C and Micro-C have uncovered chromatin loops across the genome and linked these loops to gene regulation. However, these methods only measure 3D interaction probabilities on a relative scale. Here, we overcome this limitation by using live imaging data to calibrate Micro-C in mouse embryonic stem cells, thus obtaining absolute looping probabilities for 36,804 chromatin loops across the genome. We find that the looped state is generally rare, with a mean probability of 2.3% and a maximum of 26% across the quantified loops. On average, CTCF-CTCF loops are stronger than loops between cis-regulatory elements (3.2% vs. 1.1%). Our findings can be extended to human stem cells and differentiated cells under certain assumptions. Overall, we establish an approach for genome-wide absolute loop quantification and report that loops generally occur with low probabilities, generalizing recent live imaging results to the whole genome.
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