Tri-4C: efficient and quantitative analysis of enhancer loops at hundred base pair resolution (ATAC-Seq)

Enhancer looping governs gene regulatory circuitry but is challenging to detect. Here we present Tri-4C, an ultrafine mapping method for distal chromatin contacts using triple restriction enzyme (RE) digestion. Tri-4C identifies enhancer loops that are undetectable by current single RE- based methods and reveals quantitative loop strengths in enhancer interaction networks underlying dynamic gene control. This multi-RE approach may be applied to general 3C-derived methods for accurate detection of enhancer loops. Overall design: Examination of enhancer landscape before and after IFNB1 induction IMR90 cells using ATAC seq. Examination of enhancer landscape in H7-derived vascular smooth muscle cells using ATAC seq.