摘要：SummaryEnhancer RNAs (eRNAs) are a subset of long noncoding RNA generated from genomic enhancers: they are thought to act as potent promoters of the expression of nearby genes through interaction with the transcriptional and epigenomic machineries. In the present work, we describe two eRNAs transcribed from the enhancer ofNkx2-5—a gene specifying a master cardiomyogenic lineage transcription factor (TF)—which we call Intergenic Regulatory Element Nkx2-5 Enhancers (IRENEs). TheIRENEs are encoded, respectively, on the same strand (SS) and in the divergent direction (div) respect to the nearby gene. Of note, these two eRNAs have opposing roles in the regulation ofNkx2-5:IRENE-SSacts as a canonical promoter of transcription, whereasIRENE-divrepresses the activity of the enhancer through recruitment of the histone deacetylase sirtuin 1. Thus, we have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription.Graphical AbstractDisplay OmittedHighlights•Two eRNAs (IRENE-SS,IRENE-div) with opposing functions are found upstream ofNkx2-5•IRENE-SSworks as a classical eRNA, acting as a transcriptional activator•IRENE-divacts unconventionally, functioning as a transcriptional repressor•IRENEs epigenetically control enhancer status and, subsequently, locus architectureBiological Sciences; Molecular Biology; Molecular Mechanism of Gene Regulation
