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Publication : Divergent Transcription of the Nkx2-5 Locus Generates Two Enhancer RNAs with Opposing Functions.

First Author  Salamon I Year  2020
Journal  iScience Volume  23
Issue  9 Pages  101539
PubMed ID  33083767 Mgi Jnum  J:342602
Mgi Id  MGI:7548915 Doi  10.1016/j.isci.2020.101539
Citation  Salamon I, et al. (2020) Divergent Transcription of the Nkx2-5 Locus Generates Two Enhancer RNAs with Opposing Functions. iScience 23(9):101539
abstractText  Enhancer 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 of Nkx2-5-a gene specifying a master cardiomyogenic lineage transcription factor (TF)-which we call Intergenic Regulatory Element Nkx2-5 Enhancers (IRENEs). The IRENEs 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 of Nkx2-5: IRENE-SS acts as a canonical promoter of transcription, whereas IRENE-div represses 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.
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