Cross-platform Hi-C meta-analysis identifies functional insulators that actively block enhancer-promoter interactions

However, genome-wide studies only found mild transcriptional consequences upon acute CTCF-depletion, raising confusions about how CTCF regulates enhancer-promoter (E-P) interactions and gene expression. Here we reanalyze independent Hi-C, in situ Hi-C, and micro-C data in mouse embryonic stem cells upon acute CTCF-, RAD21-, and WAPL-depletion; DeepLoop is used to enable robust comparison of orthogonal Hi-C data at kb-resolution regardless of sequencing depth.

All datasets show that most loops are lost upon CTCF depletion, but E-P interactions are enriched among the retained loops, and interestingly a small number of newly gained loops repressed by CTCF. From multiplatform Hi-C data, we identified several hundred recurrent events in which new E-P interactions form after the insulating CTCF loops disappear. We therefore define FINs (functional insulators) as CTCF sites that actively insulate their flanking sequences.