Noncoding RNA, ncRNA-a3, epigenetically regulates TAL1 transcriptional program during erythropoiesis (CUT&Run)

Here, we showed that a long non-coding RNA (lncRNA), ncRNA-a3 that is transcribed from TAL1 erythroid +51kb enhancer, is required for TAL1 activation during EPO-induced lineage commitment and formation of erythroblasts. ncRNA-a3 regulates long-range chromatin interactions between +51 enhancer, promoter and other regulatory elements in the TAL1 locus to maintain the erythroid interaction hub. By binding and recruiting p300/BRG1 to the TAL1 locus ncRNA-a3 facilitates chromatin accessibility in the TAL1 locus and activates TAL1 transcription program, including subsequent epigenetic and transcriptional activation of erythroid specific TAL1 target genes. We performed the RNA-seq, ATAC-seq, Cut&Run, NG Capture-C for WT and ncRNA-a3 KD in K562 cell lines and primary CD34+ cord blood hematopoietic cells to investigate ncRNA-a3 function during erythropoiesis