{"doi":"10.1101/270967","title":"Enhancer RNAs predict enhancer-gene regulatory links and are critical for enhancer function in neuronal systems","abstract":"<jats:p>\n                  Genomic enhancer elements regulate gene expression programs important for neuronal fate and function and are implicated in brain disease states. Enhancers undergo bidirectional transcription to generate non-coding enhancer RNAs (eRNAs). However, eRNA function remains controversial. Here, we combined ATAC-Seq and RNA-Seq datasets from three distinct neuronal culture systems in two activity states, enabling genome-wide enhancer identification and prediction of putative enhancer-gene pairs based on correlation of transcriptional output. Notably, stimulus-dependent enhancer transcription preceded mRNA induction, and CRISPR- based activation of eRNA synthesis increased mRNA at paired genes, functionally validating enhancer-gene predictions. Focusing on enhancers surrounding the\n                  <jats:italic>Fos</jats:italic>\n                  gene, we report that targeted eRNA manipulation bidirectionally modulates\n                  <jats:italic>Fos</jats:italic>\n                  mRNA, and that\n                  <jats:italic>Fos</jats:italic>\n                  eRNAs directly interact with the histone acetyltransferase domain of the enhancer-linked transcriptional co-activator CBP. Together, these results highlight the unique role of eRNAs in neuronal gene regulation and demonstrate that eRNAs can be used to identify putative target genes.\n                </jats:p>","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":null,"id":15938,"datarank":0.4443140259790559,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.15242750362075885,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.15242750362075885,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":6,"citers_with_endowment":6,"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":119584,"name":"Robert A. Phillips","orcid":"0000-0003-3560-4747","position":1,"is_corresponding":false},{"id":119585,"name":"Rhiana C. Simon","orcid":null,"position":2,"is_corresponding":false},{"id":119586,"name":"Salomon A. Roman Soto","orcid":null,"position":3,"is_corresponding":false},{"id":119587,"name":"Jenna E. Hinds","orcid":null,"position":4,"is_corresponding":false},{"id":119588,"name":"Aaron J. Salisbury","orcid":null,"position":5,"is_corresponding":false},{"id":119589,"name":"Jasmin S. Revanna","orcid":null,"position":6,"is_corresponding":false},{"id":119590,"name":"Kendra D. Bunner","orcid":null,"position":7,"is_corresponding":false},{"id":119591,"name":"Lara Ianov","orcid":"0000-0002-1859-2118","position":8,"is_corresponding":false},{"id":119592,"name":"Faraz A. Sultan","orcid":null,"position":9,"is_corresponding":false},{"id":119593,"name":"Katherine E. Savell","orcid":"0000-0001-8811-8254","position":10,"is_corresponding":false},{"id":29946,"name":"Charles A. Gersbach","orcid":"0000-0003-1478-4013","position":11,"is_corresponding":false},{"id":119594,"name":"Jeremy J. Day","orcid":"0000-0002-7361-3399","position":12,"is_corresponding":false},{"id":119582,"name":"Nancy V. N. Carullo","orcid":"0000-0001-9197-5046","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24259432","pmcid":null,"openalex_id":"https://openalex.org/W2794812371","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":1,"citation_trend":[{"year":2019,"count":3},{"year":2020,"count":1},{"year":2021,"count":2}],"oa_status":"green","license":"cc-by-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2018/07/17/270967.full.pdf","host_type":"GREEN"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2018/07/17/270967.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/270967","host_type":"publisher"},{"url":"http://iu.tind.io/record/1462","host_type":"repository"}],"fields_of_study":["Genomics and Chromatin Dynamics","RNA Research and Splicing","RNA Interference and Gene Delivery","Biology","Medicine"],"mesh_terms":[],"keywords":["Enhancer","Enhancer RNAs","Gene knockdown","Biology","Transcription (linguistics)","Gene expression","Transcription factor","Gene","RNA polymerase II","Regulation of gene expression","Messenger RNA","Chromatin","Immediate early gene","RNA","Cell biology","Promoter","Molecular biology","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T19:36:00.795964Z","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":[]}