A Super Enhancer derived enhancer RNA acts together with CTCF/Cohesin in trans to regulate erythropoiesis

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. We analyzed published RNA-seq and Promoter Capture Hi-C data from mouse fetal liver cells and embryonic stem cells to identify enhancer RNAs in erythroid cells with long-range interactions. We discovered an erythroid-specific enhancer RNA (CpoxeRNA) transcribed from an enhancer region upstream of Cpox, an enzyme important for heme synthesis. CpoxeRNA is crucial for erythropoiesis, as knockdown of CpoxeRNA results in impaired enucleation and cell proliferation during terminal erythropoiesis. CpoxeRNA interacts with cohesin and acts both in cis and in trans to regulate erythroid genes. Thus, we have identified a trans-acting eRNA, CpoxeRNA, as an important regulator of terminal erythropoiesis. Overall design: ChIRP-seq of CpoxeRNA in differentiate MEL cells