{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE243nnn/GSE243728/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":[" Genome binding/occupancy profiling by high throughput sequencing"," Third-party reanalysis","Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243728"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Cross-platform Hi-C meta-analysis identifies functional insulators that actively block enhancer-promoter interactions","description":"Insulator protein CTCF controls genome architecture through forming thousands of cohesin-dependent structural loops. 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. In CTCF-depleted cells these newly gained E-P interactions require cohesin activity. WAPL-depletion causes relaxation of FIN loops and abolish insulator functions. Importantly, CTCF-repressed genes are enriched near FINs, but CTCF-dependent genes are enriched near TAD-boundaries. We also validated the transcription regulatory functions of several FINs with CTCF-blocking assays. Taken together, DeepLoop meta-analysis unifies multiplatform Hi-C data and demonstrated that FINs, but not TAD-boundaries, are bona fide insulators.","dates":{"publication":"2026/04/10"},"accession":"GSE243728","cross_references":{"GSM":["GSM8433995","GSM8433996","GSM7794805","GSM7794804","GSM7794806","GSM8431855","GSM7794803","GSM8431854"],"GPL":["21103","17021"],"GSE":["243728"],"taxon":["Mus musculus"]}}