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The regulatory mechanisms that drive the fibrotic response in the aortic valve (AV) are poorly understood. Long noncoding RNAs derived from super-enhancers (lncRNA-SE) control gene expression and cell fate. Herein, multidimensional profiling including chromatin immunoprecipitation and sequencing, transposase-accessible chromatin sequencing, genome-wide 3D chromatin contacts of enhancer-promoter identified <jats:italic>LINC01013<\/jats:italic> as an overexpressed lncRNA-SE during CAVD. <jats:italic>LINC01013<\/jats:italic> is within a loop anchor, which has contact with the promoter of <jats:italic>CCN2 (CTGF)<\/jats:italic> located at ~180 kb upstream. Investigation showed that <jats:italic>LINC01013<\/jats:italic> acts as a decoy factor for the negative transcription elongation factor E (NELF-E), whereby it controls the expression of <jats:italic>CCN2<\/jats:italic>. <jats:italic>LINC01013-CCN2<\/jats:italic> is part of a transforming growth factor beta 1 (TGFB1) network and exerts a control over fibrogenesis. These findings illustrate a novel mechanism whereby a dysregulated lncRNA-SE controls, through a looping process, the expression of CCN2 and fibrogenesis of the AV.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010010","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T20:01:08Z","timestamp":1642536068000},"page":"e1010010","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Genome-wide chromatin contacts of super-enhancer-associated lncRNA identify LINC01013 as a regulator of fibrosis in the aortic 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