{"doi":"10.1101/2023.03.29.534720","title":"Transcription decouples estrogen-dependent changes in enhancer-promoter contact frequencies and spatial proximity","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>How enhancers regulate their target genes in the context of 3D chromatin organization is extensively studied and models which do not require direct enhancer-promoter contact have recently emerged. Here, we use the activation of estrogen receptor-dependent enhancers in a breast cancer cell line to study enhancer-promoter communication. This allows high temporal resolution tracking of molecular events from hormone stimulation to efficient gene activation. We examine how both enhancer-promoter spatial proximity assayed by DNA fluorescence in situ hybridization, and contact frequencies resulting from chromatin in situ fragmentation and proximity ligation by Capture-C, change dynamically during enhancer-driven gene activation. These orthogonal methods produce seemingly paradoxical results: upon enhancer activation enhancer-promoter contact frequencies increase while spatial proximity decreases. We explore this apparent discrepancy using different estrogen receptor ligands and transcription inhibitors. Our data demonstrate that enhancer-promoter contact frequencies are transcription independent but are influenced by enhancer-bound protein complexes whereas altered enhancer-promoter proximity depends on transcription. Our results emphasize that the relationship between contact frequencies and physical distance in the nucleus, especially over short genomic distances, is not always a simple one.</jats:p>","journal":null,"year":null,"id":599951,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1537833,"name":"Ilya Flyamer","orcid":null,"position":1,"is_corresponding":false},{"id":192333,"name":"Shelagh Boyle","orcid":null,"position":2,"is_corresponding":false},{"id":1537834,"name":"Elias Friman","orcid":"0000-0001-9944-6560","position":3,"is_corresponding":false},{"id":65653,"name":"Wendy A. Bickmore","orcid":"0000-0001-6660-7735","position":4,"is_corresponding":false},{"id":1537832,"name":"Luciana I. Gómez Acuña","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Transcription decouples estrogen-dependent changes in enhancer-promoter contact frequencies and spatial proximity","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>How enhancers regulate their target genes in the context of 3D chromatin organization is extensively studied and models which do not require direct enhancer-promoter contact have recently emerged. Here, we use the activation of estrogen receptor-dependent enhancers in a breast cancer cell line to study enhancer-promoter communication. This allows high temporal resolution tracking of molecular events from hormone stimulation to efficient gene activation. We examine how both enhancer-promoter spatial proximity assayed by DNA fluorescence in situ hybridization, and contact frequencies resulting from chromatin in situ fragmentation and proximity ligation by Capture-C, change dynamically during enhancer-driven gene activation. These orthogonal methods produce seemingly paradoxical results: upon enhancer activation enhancer-promoter contact frequencies increase while spatial proximity decreases. We explore this apparent discrepancy using different estrogen receptor ligands and transcription inhibitors. Our data demonstrate that enhancer-promoter contact frequencies are transcription independent but are influenced by enhancer-bound protein complexes whereas altered enhancer-promoter proximity depends on transcription. Our results emphasize that the relationship between contact frequencies and physical distance in the nucleus, especially over short genomic distances, is not always a simple one.</jats:p>","is_dataset_classified":null,"base_score":2.70805020110221,"endowment":2.70805020110221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23304386","pmcid":null,"openalex_id":"https://openalex.org/W4361277650","authors":[],"funders":[{"funder_name":"Swiss National Science Foundation","grant_id":"206805","title":"Exploring cohesin-driven ultra-long-range chromatin interactions between transcriptional regulatory elements"},{"funder_name":"UK Research and Innovation","grant_id":"MC_UU_00035/7","title":"Enhancer function and dysfunction: molecular mechanisms, genome context, and disease"},{"funder_name":"UK Research and Innovation","grant_id":"MC_UU_00007/2","title":"The role of spatial nuclear organisation in\ngenome function"}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2023,"count":3},{"year":2024,"count":6},{"year":2025,"count":5}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2023/03/29/2023.03.29.534720.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2023/03/29/2023.03.29.534720.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2023.03.29.534720","host_type":"publisher"},{"url":"https://doi.org/10.1101/2023.03.29.534720","host_type":"repository"},{"url":"https://europepmc.org/article/PPR/PPR638395","host_type":"Europe_PMC"},{"url":"https://europepmc.org/api/fulltextRepo?pprId=PPR638395&type=FILE&fileName=EMS173319-pdf.pdf&mimeType=application/pdf","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1371/journal.pgen.1011277","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/38781242","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pgen.1011277","host_type":""},{"url":"https://doaj.org/article/387f06a75f744698b89a409bd7dfbca0","host_type":""},{"url":"https://hdl.handle.net/20.500.11820/89a5f423-1bed-46db-9e3a-80fba116403a","host_type":""},{"url":"https://www.pure.ed.ac.uk/ws/files/445614546/journal.pgen.1011277_1_.pdf","host_type":""},{"url":"https://www.research.ed.ac.uk/en/publications/89a5f423-1bed-46db-9e3a-80fba116403a","host_type":""},{"url":"https://www.pure.ed.ac.uk/ws/files/442520160/journal.pgen.1011277.pdf","host_type":""},{"url":"https://www.pure.ed.ac.uk/ws/files/440596132/PGENETICS-D-23-01311_accepted.pdf","host_type":""}],"fields_of_study":["Genomics and Chromatin Dynamics","RNA Research and Splicing","Plant Molecular Biology Research","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Enhancer","Enhancer RNAs","Chromatin","Promoter","Biology","Chromosome conformation capture","Estrogen receptor alpha","Transcription (linguistics)","Transcription factor","Regulation of gene expression","Estrogen receptor","Gene","Molecular biology","Gene expression","Genetics","Transcriptional Activation","Transcription, Genetic","Estrogens","Breast Neoplasms","QH426-470","Gene Expression Regulation, Neoplastic","Enhancer Elements, Genetic","Receptors, Estrogen","Cell Line, Tumor","MCF-7 Cells","Humans","Female","Promoter Regions, Genetic","In Situ Hybridization, Fluorescence","Research Article"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"arrayexpress"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T11:46:36.298364Z","pmid":null,"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":[]}