A Super Enhancer-Derived Enhancer RNA Acts Together with CTCF/Cohesin in Trans to Regulate Erythropoiesis

<b>Background/Objectives</b>: Enhancer RNAs (eRNAs) function in diverse modes and increasing studies have shown that they play important roles in normal development and disease. However, their role in erythropoiesis is not fully understood. <b>Methods</b>: We analyzed published RNA-seq and Promoter Capture Hi-C data from mouse E14.5 fetal liver cells to identify enhancer RNAs in erythroid cells with long-range interactions. <b>Results</b>: We discovered an erythroid-specific enhancer RNA (<i>CpoxeRNA</i>) transcribed from an enhancer region upstream of <i>Cpox</i>, an enzyme important for heme synthesis. <i>CpoxeRNA</i> is important for erythropoiesis, as the knockdown of <i>CpoxeRNA</i> by shRNA results in impaired enucleation and cell proliferation during terminal differentiation. <i>CpoxeRNA</i> interacts with cohesin and acts both <i>in cis</i> and <i>trans</i> to regulate erythroid genes. <b>Conclusions</b>: we have identified a <i>trans-acting</i> eRNA, <i>CpoxeRNA</i>, as a potential regulator of terminal erythropoiesis.