{"doi":"10.1101/gr.276643.122","title":"Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries","abstract":"Vertebrate genomes are partitioned into chromatin domains or topologically associating domains (TADs), which are typically bound by head-to-head pairs of CTCF binding sites. Transcription at domain boundaries correlates with better insulation; however, it is not known whether the boundary transcripts themselves contribute to boundary function. Here we characterize boundary-associated RNAs genome-wide, focusing on the disease-relevant INK4a/ARF and MYC TAD. Using CTCF site deletions and boundary-associated RNA knockdowns, we observe that boundary-associated RNAs facilitate recruitment and clustering of CTCF at TAD borders. The resulting CTCF enrichment enhances TAD insulation, enhancer–promoter interactions, and TAD gene expression. Importantly, knockdown of boundary-associated RNAs results in loss of boundary insulation function. Using enhancer deletions and CRISPRi of promoters, we show that active TAD enhancers, but not promoters, induce boundary-associated RNA transcription, thus defining a novel class of regulatory enhancer RNAs.","journal":"Genome Research","year":2023,"id":389421,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":335751,"name":"Bharath Saravanan","orcid":null,"position":1,"is_corresponding":false},{"id":334588,"name":"Kaivalya Walavalkar","orcid":"0000-0002-5097-524X","position":2,"is_corresponding":false},{"id":334587,"name":"Umer Farooq","orcid":"0000-0001-8371-6140","position":3,"is_corresponding":false},{"id":334590,"name":"Anurag Kumar Singh","orcid":"0000-0003-0818-0993","position":4,"is_corresponding":false},{"id":13154,"name":"Radhakrishnan Sabarinathan","orcid":"0000-0001-8916-3954","position":5,"is_corresponding":false},{"id":317049,"name":"Jitendra Thakur","orcid":"0000-0002-1895-6719","position":6,"is_corresponding":false},{"id":1159740,"name":"Awadhesh Pandit","orcid":"0000-0001-5043-6855","position":7,"is_corresponding":false},{"id":45084,"name":"Steven Henikoff","orcid":"0000-0002-7621-8685","position":8,"is_corresponding":false},{"id":95972,"name":"Dimple Notani","orcid":"0000-0002-9460-8070","position":9,"is_corresponding":false},{"id":335753,"name":"Zubairul Islam","orcid":null,"position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T01:18:27.054415Z","pmid":"36650052","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}