{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Islam Z"],"funding":["Wellcome-IA","CSIR-SPM","Department of Science and Technology","Department of Atomic Energy","Council of Scientific and Industrial Research","TIFR-NCBS","National Center for Biological Sciences–Tata Institute of Fundamental Research","Wellcome Trust","NCBS-TIFR"],"pagination":["1-17"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9977152"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["33(1)"],"pubmed_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 <i>INK4a/ARF</i> and <i>MYC</i> 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"],"pubmed_title":["Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries."],"pmcid":["PMC9977152"],"funding_grant_id":["CRG/2019/005714","CSIR","12-R&amp;D-TFR-5.04-0800","IA/1/14/2/501539"],"pubmed_authors":["Walavalkar K","Singh AK","Pandit A","Saravanan B","Henikoff S","Notani D","Farooq U","Islam Z","Thakur J","Radhakrishnan S"],"additional_accession":[]},"is_claimable":false,"name":"Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries.","description":"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 <i>INK4a/ARF</i> and <i>MYC</i> 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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-28T08:08:53.715Z","creation":"2025-04-04T08:35:44.522Z"},"accession":"S-EPMC9977152","cross_references":{"pubmed":["36650052"],"doi":["10.1101/gr.276643.122"]}}