Genome-wide absolute quantification of chromatin looping

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. Competing Interest Statement The authors have declared no competing interest.