{"doi":"10.1093/nar/gkaa671","title":"Enhancer RNAs predict enhancer–gene regulatory links and are critical for enhancer function in neuronal systems","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>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 Assay for Transposase-Accessible Chromatin using Sequencing (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 Fos gene, we report that targeted eRNA manipulation bidirectionally modulates Fos mRNA, and that Fos eRNAs directly interact with the histone acetyltransferase domain of the enhancer-linked transcriptional co-activator CREB-binding protein (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.</jats:p>","journal":"Nucleic Acids Research","year":2020,"id":15960,"datarank":2.5712327091985467,"base_score":4.912654885736052,"endowment":4.912654885736052,"self_citation_contribution":0.736898232860408,"citation_network_contribution":1.8343344763381388,"self_endowment_contribution":0.736898232860408,"citer_contribution":1.8343344763381388,"corpus_percentile":null,"corpus_rank":null,"citation_count":135,"citer_count":101,"citers_with_citation_signal":83,"citers_with_endowment":83,"datacite_reuse_total":25,"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":119652,"name":"Robert A Phillips III","orcid":null,"position":1,"is_corresponding":false},{"id":119653,"name":"Rhiana C Simon","orcid":null,"position":2,"is_corresponding":false},{"id":119654,"name":"Salomon A Roman Soto","orcid":null,"position":3,"is_corresponding":false},{"id":119655,"name":"Jenna E Hinds","orcid":null,"position":4,"is_corresponding":false},{"id":119656,"name":"Aaron J Salisbury","orcid":null,"position":5,"is_corresponding":false},{"id":119657,"name":"Jasmin S Revanna","orcid":null,"position":6,"is_corresponding":false},{"id":119658,"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":119659,"name":"Faraz A Sultan","orcid":null,"position":9,"is_corresponding":false},{"id":119660,"name":"Katherine E Savell","orcid":null,"position":10,"is_corresponding":false},{"id":119661,"name":"Charles A Gersbach","orcid":null,"position":11,"is_corresponding":false},{"id":119594,"name":"Jeremy J. Day","orcid":"0000-0002-7361-3399","position":12,"is_corresponding":false},{"id":119651,"name":"Nancy V N Carullo","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.912654885736052,"endowment":4.912654885736052,"datacite_reuse_total":25,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32810208","pmcid":"PMC7515708","openalex_id":"https://openalex.org/W3069949010","authors":[],"funders":[{"funder_name":"NIH","grant_id":"MH114990","title":null},{"funder_name":"NIH","grant_id":"DA039650","title":null},{"funder_name":"NIH","grant_id":"DA034681","title":null},{"funder_name":"UAB","grant_id":"R21DA041878","title":null},{"funder_name":"UAB","grant_id":"R01DA036865","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"DP1 DA039650","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"K99 DA034681","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"R01 MH114990","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"R21 DA048348","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"R00 DA034681","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"F31 DA042514","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R21DA041878-02","title":"In Vivo Epigenome Editing with CRISPR-Based Histone Acetyltransferase Transgenic Mice"},{"funder_name":"National Institutes of Health","grant_id":"5R01MH114990-05","title":"Enhancer RNA Regulation of Experience-dependent Neuroepigenetic Processes"},{"funder_name":"National Institutes of Health","grant_id":"5R01DA036865-02","title":"Engineering Targeted Epigenetic Modifiers for Precise Control of Gene Regulation"},{"funder_name":"Paul G. Allen Frontiers Group","grant_id":"","title":null},{"funder_name":"Allen Distinguished Investigator Award","grant_id":"","title":null},{"funder_name":"CIRC Emerging Scholar Award","grant_id":"","title":null}],"total_grants":17,"fwci":5.668,"citation_percentile":0.9713184,"influential_citations":5,"citation_trend":[{"year":2020,"count":5},{"year":2021,"count":18},{"year":2022,"count":18},{"year":2023,"count":27},{"year":2024,"count":35},{"year":2025,"count":25},{"year":2026,"count":7}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://academic.oup.com/nar/article-pdf/48/17/9550/33787086/gkaa671.pdf","host_type":"journal"},{"url":"https://academic.oup.com/nar/article-pdf/48/17/9550/33787086/gkaa671.pdf","host_type":"GOLD"},{"url":"https://academic.oup.com/nar/article-pdf/48/17/9550/33787086/gkaa671.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/nar/article-pdf/48/17/9550/33787086/gkaa671.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/nar/gkaa671","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32810208","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7515708","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7515708","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7515708?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/270967","host_type":""},{"url":"http://dx.doi.org/10.1093/nar/gkaa671","host_type":""},{"url":"https://dx.doi.org/10.1101/270967","host_type":""},{"url":"https://dx.doi.org/10.1093/nar/gkaa671","host_type":""}],"fields_of_study":["RNA Research and Splicing","Genomics and Chromatin Dynamics","Cancer-related molecular mechanisms research","Medicine","Biology","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","CREB-Binding Protein","CRISPR-Cas Systems","Cells, Cultured","Chromatin","Enhancer Elements, Genetic","Gene Expression Regulation","HEK293 Cells","Humans","Neurons","Proto-Oncogene Proteins c-fos","RNA","RNA, Messenger","RNA, Small Interfering","Rats","Reproducibility of Results","Sequence Analysis, RNA","Single Molecule Imaging"],"mesh_terms":["Single Molecule Imaging","Animals","Cells, Cultured","Chromatin","Enhancer Elements, Genetic","Gene Expression Regulation","Humans","Neurons","RNA","RNA, Messenger","Reproducibility of Results","Proto-Oncogene Proteins c-fos","Sequence Analysis, RNA","RNA, Small Interfering","CREB-Binding Protein","Rats","HEK293 Cells","CRISPR-Cas Systems"],"keywords":["Enhancer","Enhancer RNAs","Biology","Gene","Regulation of gene expression","Chromatin","RNA polymerase II","Enhancer trap","Gene expression","Genetics","Transcription factor","Cell biology","Promoter","Neurons","Sequence Analysis, RNA","Gene regulation, Chromatin and Epigenetics","Reproducibility of Results","CREB-Binding Protein","Single Molecule Imaging","Rats","Enhancer Elements, Genetic","HEK293 Cells","Gene Expression Regulation","Animals","Humans","RNA","RNA, Messenger","CRISPR-Cas Systems","RNA, Small Interfering","Proto-Oncogene Proteins c-fos","Cells, Cultured"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.16960406.v1","title":"Additional file 1 of An explainable artificial intelligence approach for decoding the enhancer histone modifications code and identification of novel enhancers in Drosophila","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.16960406","title":"Additional file 1 of An explainable artificial intelligence approach for decoding the enhancer histone modifications code and identification of novel enhancers in Drosophila","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.16960409.v1","title":"Additional file 2 of An explainable artificial intelligence approach for decoding the enhancer histone modifications code and identification of novel enhancers in Drosophila","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.16960409","title":"Additional file 2 of An explainable artificial intelligence approach for decoding the enhancer histone modifications code and identification of novel enhancers in Drosophila","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22721513.v1","title":"Additional file 1 of An optimized approach for multiplexing single-nuclear ATAC-seq using oligonucleotide-conjugated antibodies","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22721513","title":"Additional file 1 of An optimized approach for multiplexing single-nuclear ATAC-seq using oligonucleotide-conjugated antibodies","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22721516.v1","title":"Additional file 2 of An optimized approach for multiplexing single-nuclear ATAC-seq using oligonucleotide-conjugated antibodies","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22721516","title":"Additional file 2 of An optimized approach for multiplexing single-nuclear ATAC-seq using oligonucleotide-conjugated antibodies","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.25572518.v1","title":"Additional file 1 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.25572518","title":"Additional file 1 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26704161","title":"Additional file 21 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704161.v1","title":"Additional file 21 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704158","title":"Additional file 20 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704158.v1","title":"Additional file 20 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704155","title":"Additional file 19 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704149","title":"Additional file 17 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26704152.v1","title":"Additional file 18 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704155.v1","title":"Additional file 19 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704146","title":"Additional file 16 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704149.v1","title":"Additional file 17 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26704152","title":"Additional file 18 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704137","title":"Additional file 13 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26704140.v1","title":"Additional file 14 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26704143","title":"Additional file 15 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26704143.v1","title":"Additional file 15 of Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs","publisher":"figshare","resource_type":"Image"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"cellosaurus"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T19:39:22.437007Z","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":[]}