{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:21:47Z","timestamp":1787570507309,"version":"build-2736575974"},"reference-count":70,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["Postdoctoral fellowship 1-19-PDF-117"],"award-info":[{"award-number":["Postdoctoral fellowship 1-19-PDF-117"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"John and Rebekah Harper","award":["Graduate student fellowship"],"award-info":[{"award-number":["Graduate student fellowship"]}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RR 160083"],"award-info":[{"award-number":["RR 160083"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["AU-2000-20220331"],"award-info":[{"award-number":["AU-2000-20220331"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM136922"],"award-info":[{"award-number":["R01GM136922"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K22CA204468"],"award-info":[{"award-number":["K22CA204468"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK062777"],"award-info":[{"award-number":["R01 DK062777"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK095842"],"award-info":[{"award-number":["R01 DK095842"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006988","name":"John S. Dunn Foundation","doi-asserted-by":"publisher","award":["Collaborative research award 2019"],"award-info":[{"award-number":["Collaborative research award 2019"]}],"id":[{"id":"10.13039\/100006988","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The nuclear receptor, farnesoid X receptor (FXR\/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein-coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and global run-on sequencing (GRO-seq) analyses in mouse liver, we found that FXR activation affects the expression of many RNA transcripts from chromatin regions bearing enhancer features. Among these we discovered a previously unannotated liver-enriched enhancer-derived lncRNA (eRNA), termed FXR-induced non-coding RNA (\n                    <jats:italic>Fincor<\/jats:italic>\n                    ). We show that\n                    <jats:italic>Fincor<\/jats:italic>\n                    is specifically induced by the hammerhead-type FXR agonists, including GW4064 and tropifexor. CRISPR\/Cas9-mediated liver-specific knockdown of\n                    <jats:italic>Fincor<\/jats:italic>\n                    in dietary NASH mice reduced the beneficial effects of tropifexor, an FXR agonist currently in clinical trials for NASH and primary biliary cholangitis (PBC), indicating that amelioration of liver fibrosis and inflammation in NASH treatment by tropifexor is mediated in part by\n                    <jats:italic>Fincor<\/jats:italic>\n                    . Overall, our findings highlight that pharmacological activation of FXR by hammerhead-type agonists induces a novel eRNA,\n                    <jats:italic>Fincor<\/jats:italic>\n                    , contributing to the amelioration of NASH in mice.\n                    <jats:italic>Fincor<\/jats:italic>\n                    may represent a new drug target for addressing metabolic disorders, including NASH.\n                  <\/jats:p>","DOI":"10.7554\/elife.91438","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T12:25:09Z","timestamp":1705580709000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.91438","source":"Crossref","is-referenced-by-count":7,"title":["Hammerhead-type FXR agonists induce an enhancer RNA Fincor that ameliorates nonalcoholic steatohepatitis in mice"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0612-8553","authenticated-orcid":true,"given":"Jinjing","family":"Chen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign","place":["Urbana, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3644-1284","authenticated-orcid":true,"given":"Ruoyu","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gds6c39","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Feng","family":"Xiong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gds6c39","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign","place":["Urbana, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Byron","family":"Kemper","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign","place":["Urbana, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9042-5664","authenticated-orcid":true,"given":"Wenbo","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gds6c39","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center","place":["Houston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-0286","authenticated-orcid":true,"given":"Jongsook","family":"Kemper","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign","place":["Urbana, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"4911","DOI":"10.1016\/j.bmcl.2010.06.084","type":"journal-article","article-title":"Synthesis and pharmacological validation of a novel series of non-steroidal FXR agonists","volume":"20","author":"Abel","year":"2010","journal-title":"Bioorganic & Medicinal Chemistry Letters"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.3390\/ph11040104","type":"journal-article","article-title":"Obeticholic acid: A new era in the treatment of nonalcoholic fatty liver disease","volume":"11","author":"Abenavoli","year":"2018","journal-title":"Pharmaceuticals"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2305-5839.2014.12.06","type":"journal-article","article-title":"Recent advances in the development of farnesoid X receptor agonists","volume":"3","author":"Ali","year":"2015","journal-title":"Annals of Translational Medicine"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"R91","DOI":"10.1530\/ERC-11-0041","type":"journal-article","article-title":"The RNA-binding protein Sam68 is a multifunctional player in human cancer","volume":"18","author":"Bielli","year":"2011","journal-title":"Endocrine-Related Cancer"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19554-7","type":"journal-article","article-title":"Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting","volume":"11","author":"Brocker","year":"2020","journal-title":"Nature Communications"},{"key":"bib6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04697-5","type":"journal-article","article-title":"Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis","volume":"9","author":"Byun","year":"2018","journal-title":"Nature Communications"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14384-z","type":"journal-article","article-title":"Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase","volume":"11","author":"Byun","year":"2020","journal-title":"Nature Communications"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nrm3312","type":"journal-article","article-title":"Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR","volume":"13","author":"Calkin","year":"2012","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.cell.2014.03.008","type":"journal-article","article-title":"The noncoding RNA revolution-trashing old rules to forge new ones","volume":"157","author":"Cech","year":"2014","journal-title":"Cell"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"4132","DOI":"10.4049\/jimmunol.1502261","type":"journal-article","article-title":"BET inhibition attenuates helicobacter pylori-induced inflammatory response by suppressing inflammatory gene transcription and enhancer activation","volume":"196","author":"Chen","year":"2016","journal-title":"Journal of Immunology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1161\/01.ATV.0000178994.21828.a7","type":"journal-article","article-title":"The Farnesoid X receptor: A molecular link between bile acid and lipid and glucose metabolism","volume":"25","author":"Claudel","year":"2005","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","type":"journal-article","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/s1097-2765(03)00104-7","type":"journal-article","article-title":"A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR","volume":"11","author":"Downes","year":"2003","journal-title":"Molecular Cell"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.cell.2014.03.012","type":"journal-article","article-title":"Nuclear receptors, RXR, and the big bang","volume":"157","author":"Evans","year":"2014","journal-title":"Cell"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1016\/j.cell.2014.10.022","type":"journal-article","article-title":"Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo","volume":"159","author":"Fang","year":"2014","journal-title":"Cell"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nm.3760","type":"journal-article","article-title":"Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance","volume":"21","author":"Fang","year":"2015","journal-title":"Nature Medicine"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","type":"journal-article","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nature Medicine"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/nrg3813","type":"journal-article","article-title":"A census of human RNA-binding proteins","volume":"15","author":"Gerstberger","year":"2014","journal-title":"Nature Reviews. Genetics"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baw035","type":"journal-article","article-title":"ATtRACT\u2014a database of RNA-binding proteins and associated motifs","volume":"2016","author":"Giudice","year":"2016","journal-title":"Database"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/s1097-2765(00)00051-4","type":"journal-article","article-title":"A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis","volume":"6","author":"Goodwin","year":"2000","journal-title":"Molecular Cell"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","type":"journal-article","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Molecular Cell"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1002\/hep4.1368","type":"journal-article","article-title":"Tropifexor-mediated abrogation of steatohepatitis and fibrosis is associated with the antioxidative gene expression profile in rodents","volume":"3","author":"Hernandez","year":"2019","journal-title":"Hepatology Communications"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1038\/s41588-019-0485-9","type":"journal-article","article-title":"NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements","volume":"51","author":"Hirabayashi","year":"2019","journal-title":"Nature Genetics"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/nature21374","type":"journal-article","article-title":"An atlas of human long non-coding RNAs with accurate 5\u2019 ends","volume":"543","author":"Hon","year":"2017","journal-title":"Nature"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"7319","DOI":"10.1073\/pnas.1324151111","type":"journal-article","article-title":"Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation","volume":"111","author":"Hsieh","year":"2014","journal-title":"PNAS"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.141640","type":"journal-article","article-title":"BRD4 inhibition and FXR activation, individually beneficial in cholestasis, are antagonistic in combination","volume":"6","author":"Jung","year":"2020","journal-title":"JCI Insight"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/hep.27677","type":"journal-article","article-title":"Farnesoid X receptor-induced lysine-specific histone demethylase reduces hepatic bile acid levels and protects the liver against bile acid toxicity","volume":"62","author":"Kim","year":"2015","journal-title":"Hepatology"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12179","type":"journal-article","article-title":"Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis","volume":"7","author":"Kim","year":"2016","journal-title":"Nature Communications"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1002\/hep.30966","type":"journal-article","article-title":"MicroRNA-210 promotes bile acid-induced cholestatic liver injury by targeting mixed-lineage leukemia-4 methyltransferase in mice","volume":"71","author":"Kim","year":"2020","journal-title":"Hepatology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1042\/BCJ20170956","type":"journal-article","article-title":"Y-box proteins combine versatile cold shock domains and arginine-rich motifs (ARMs) for pleiotropic functions in RNA biology","volume":"475","author":"Kleene","year":"2018","journal-title":"The Biochemical Journal"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1159\/000371670","type":"journal-article","article-title":"Bile acids as hormones: The FXR-FGF15\/19 pathway","volume":"33","author":"Kliewer","year":"2015","journal-title":"Digestive Diseases"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jhep.2021.03.020","type":"journal-article","article-title":"FXR agonists for NASH: How are they different and what difference do they make?","volume":"75","author":"Kremoser","year":"2021","journal-title":"Journal of Hepatology"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.gde.2013.11.017","type":"journal-article","article-title":"Enhancer RNAs: The new molecules of transcription","volume":"25","author":"Lai","year":"2014","journal-title":"Current Opinion in Genetics & Development"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.tibs.2014.02.007","type":"journal-article","article-title":"Enhancer RNAs and regulated transcriptional programs","volume":"39","author":"Lam","year":"2014","journal-title":"Trends in Biochemical Sciences"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.tibs.2006.08.002","type":"journal-article","article-title":"FXR, a multipurpose nuclear receptor","volume":"31","author":"Lee","year":"2006","journal-title":"Trends in Biochemical Sciences"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"12604","DOI":"10.1074\/jbc.M109.094524","type":"journal-article","article-title":"A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via MicroRNA-34a inhibition","volume":"285","author":"Lee","year":"2010","journal-title":"Journal of Biological Chemistry"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/hep.25609","type":"journal-article","article-title":"Genomic analysis of hepatic farnesoid X receptor binding sites reveals altered binding in obesity and direct gene repression by farnesoid X receptor in mice","volume":"56","author":"Lee","year":"2012","journal-title":"Hepatology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature13961","type":"journal-article","article-title":"Nutrient-sensing nuclear receptors coordinate autophagy","volume":"516","author":"Lee","year":"2014","journal-title":"Nature"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/nature12210","type":"journal-article","article-title":"Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation","volume":"498","author":"Li","year":"2013","journal-title":"Nature"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nrg.2016.4","type":"journal-article","article-title":"Enhancers as non-coding RNA transcription units: Recent insights and future perspectives","volume":"17","author":"Li","year":"2016","journal-title":"Nature Reviews. Genetics"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1093\/toxsci\/kfx078","type":"journal-article","article-title":"Sortilin 1 loss-of-function protects against cholestatic liver injury by attenuating hepatic bile acid accumulation in bile duct ligated mice","volume":"161","author":"Li","year":"2018","journal-title":"Toxicological Sciences"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1126\/science.aba4991","type":"journal-article","article-title":"A noncoding RNA modulator potentiates phenylalanine metabolism in mice","volume":"373","author":"Li","year":"2021","journal-title":"Science"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","type":"journal-article","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41580-022-00566-8","type":"journal-article","article-title":"Long non-coding RNAs: definitions, functions, challenges and recommendations","volume":"24","author":"Mattick","year":"2023","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1161\/CIRCULATIONAHA.118.036769","type":"journal-article","article-title":"Inhibition of the hypoxia-inducible factor 1\u03b1-induced cardiospecific HERNA1 enhance-templated RNA protects from heart disease","volume":"139","author":"Mirtschink","year":"2019","journal-title":"Circulation"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1038\/s41586-021-03577-1","type":"journal-article","article-title":"Enhancer release and retargeting activates disease-susceptibility genes","volume":"595","author":"Oh","year":"2021","journal-title":"Nature"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/s41594-018-0102-0","type":"journal-article","article-title":"RNAs interact with BRD4 to promote enhanced chromatin engagement and transcription activation","volume":"25","author":"Rahnamoun","year":"2018","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/nature17674","type":"journal-article","article-title":"Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis","volume":"534","author":"Sallam","year":"2016","journal-title":"Nature"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/s41591-022-02200-8","type":"journal-article","article-title":"Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a\/b trial","volume":"29","author":"Sanyal","year":"2023","journal-title":"Nature Medicine"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/s41594-020-0446-0","type":"journal-article","article-title":"Enhancer RNAs are an important regulatory layer of the epigenome","volume":"27","author":"Sartorelli","year":"2020","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nature13949","type":"journal-article","article-title":"Transcriptional regulation of autophagy by an FXR-CREB axis","volume":"516","author":"Seok","year":"2014","journal-title":"Nature"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"3144","DOI":"10.1172\/JCI97736","type":"journal-article","article-title":"Fasting-induced JMJD3 histone demethylase epigenetically activates mitochondrial fatty acid \u03b2-oxidation","volume":"128","author":"Seok","year":"2018","journal-title":"The Journal of Clinical Investigation"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"733","DOI":"10.2337\/db20-0856","type":"journal-article","article-title":"Defective FXR-SHP regulation in obesity aberrantly increases miR-802 expression, promoting insulin resistance and fatty liver","volume":"70","author":"Seok","year":"2021","journal-title":"Diabetes"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41580-020-00315-9","type":"journal-article","article-title":"Gene regulation by long non-coding RNAs and its biological functions","volume":"22","author":"Statello","year":"2021","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2022.101603","type":"journal-article","article-title":"Obesity-induced miR-802 directly targets AMPK and promotes nonalcoholic steatohepatitis in mice","volume":"66","author":"Sun","year":"2022","journal-title":"Molecular Metabolism"},{"key":"bib56","doi-asserted-by":"publisher","DOI":"10.1172\/JCI161759","type":"journal-article","article-title":"Long noncoding RNA LEENE promotes angiogenesis and ischemic recovery in diabetes models","volume":"133","author":"Tang","year":"2023","journal-title":"The Journal of Clinical Investigation"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1002\/hep.23450","type":"journal-article","article-title":"Genome-wide tissue-specific farnesoid X receptor binding in mouse liver and intestine","volume":"51","author":"Thomas","year":"2010","journal-title":"Hepatology"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"9960","DOI":"10.1021\/acs.jmedchem.7b00907","type":"journal-article","article-title":"Discovery of tropifexor (LJN452), a highly potent non-bile acid FXR agonist for the treatment of cholestatic liver diseases and nonalcoholic steatohepatitis (NASH)","volume":"60","author":"Tully","year":"2017","journal-title":"Journal of Medicinal Chemistry"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","type":"journal-article","article-title":"Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism","volume":"24","author":"Wahlstr\u00f6m","year":"2016","journal-title":"Cell Metabolism"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1002\/hep.22519","type":"journal-article","article-title":"Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response","volume":"48","author":"Wang","year":"2008","journal-title":"Hepatology"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1407-6","type":"journal-article","article-title":"BCL-2 family isoforms in apoptosis and cancer","volume":"10","author":"Warren","year":"2019","journal-title":"Cell Death & Disease"},{"key":"bib62","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05383-2","type":"journal-article","article-title":"Long noncoding RNA licensing of obesity-linked hepatic lipogenesis and NAFLD pathogenesis","volume":"9","author":"Zhao","year":"2018","journal-title":"Nature Communications"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"12535","DOI":"10.1074\/jbc.RA118.004188","type":"journal-article","article-title":"Structural insights into the heterodimeric complex of the nuclear receptors FXR and RXR","volume":"293","author":"Zheng","year":"2018","journal-title":"The Journal of Biological Chemistry"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s00018-020-03593-w","type":"journal-article","article-title":"RBM38 in cancer: role and mechanism","volume":"78","author":"Zou","year":"2021","journal-title":"Cellular and Molecular Life Sciences"},{"key":"dataset1","type":"dataset","article-title":"An FXR-induced novel enhancer RNA, Fincor","volume-title":"NCBI Gene Expression Omnibus","author":"Chen","year":"2024","unstructured":"Chen J, Wang R, Xiong F, Sun H, Kemper B, Li W, Kemper JK. 2024. An FXR-induced novel enhancer RNA, Fincor. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE221986. GSE221986."},{"key":"dataset2","type":"dataset","article-title":"Genome-wide profiling of LXR, RXR and PPAR\u03b1 in mouse liver reveals extensive sharing of binding sites","volume-title":"NCBI Gene Expression Omnibus","author":"Boergesen","year":"2012","unstructured":"Boergesen M, Gross B, van Heeringen SJ, Hagenbeek D, Bindesb\u00f8ll C, Caron S, Lalloyer F, Steffensen KR, Nebb HI, Stunnenberg HG, Staels B, Mandrup S. 2012. Genome-wide profiling of LXR, RXR and PPAR\u03b1 in mouse liver reveals extensive sharing of binding sites. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE35262. GSE35262."},{"key":"dataset3","type":"dataset","article-title":"Pioneer transcription factor FoxA maintains an accessible nucleosome configuration at enhancers for tissue-specific gene activation [ChIP-seq]","volume-title":"NCBI Gene Expression Omnibus","author":"Iwafuchi-Doi","year":"2016","unstructured":"Iwafuchi-Doi M, Donahue G, Kakumanu A, Watts JA, Mahony S, Pugh BF, Lee D, Kaestner KH, Zaret KS. 2016. Pioneer transcription factor FoxA maintains an accessible nucleosome configuration at enhancers for tissue-specific gene activation [ChIP-seq]. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE77670. GSE77670."},{"key":"dataset4","type":"dataset","article-title":"H3K27ac ChIP-Seq","volume-title":"ENCODE","author":"ENCODE consortium","year":"2011","unstructured":"ENCODE consortium. 2011. H3K27ac ChIP-Seq. ENCODE. https:\/\/www.encodeproject.org\/files\/ENCFF001KMI\/. ENCFF001KMI."},{"key":"dataset5","type":"dataset","article-title":"H3K4me1 ChIP-Seq","volume-title":"ENCODE","author":"ENCODE consortium","year":"2011","unstructured":"ENCODE consortium. 2011. H3K4me1 ChIP-Seq. ENCODE. https:\/\/www.encodeproject.org\/files\/ENCFF001KNF\/. ENCFF001KNF."},{"key":"dataset6","type":"dataset","article-title":"FXR liver ChIP-Seq","volume-title":"UCSC","author":"Thomas","year":"2010","unstructured":"Thomas AM, Hart SN, Kong B, Fang J, Zhong XB, Guo GL. 2010. FXR liver ChIP-Seq. UCSC. https:\/\/genome.ucsc.edu\/goldenPath\/customTracks\/custTracks.html. mouse genome."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/91438\/elife-91438-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/91438\/elife-91438-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/91438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:36:55Z","timestamp":1787567815000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/91438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,15]]},"references-count":70,"alternative-id":["10.7554\/eLife.91438"],"URL":"https:\/\/doi.org\/10.7554\/elife.91438","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.20.567833","asserted-by":"subject"}],"references":[{"id-type":"accession","id":"GSE35262","asserted-by":"subject"},{"id-type":"accession","id":"GSE77670","asserted-by":"subject"},{"id-type":"accession","id":"ENCFF001KMI","asserted-by":"subject"},{"id-type":"accession","id":"ENCFF001KNF","asserted-by":"subject"},{"id-type":"accession","id":"mouse genome","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.91438.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.91438.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.91438.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE221986","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,15]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP91438"}}