Noncoding RNA, , Epigenetically Regulates TAL1 Transcriptional Program During Erythropoiesis.

Hematopoietic transcription is a combinatorial control of transcription factors, chromatin modifiers, and non-coding RNAs. TAL1 is a critical regulator of normal and malignant hematopoiesis. However, mechanism underlying regulation of TAL1 activity during erythropoiesis versus leukemogenesis remains elusive. Here, we showed that an enhancer RNA, transcribed from Kb-enhancer, is positively correlated with locus chromatin accessibility and transcription, and required for activation during EPO-induced erythropoiesis. Loss of in CD34 hematopoietic stem and progenitor cells leads to reduction of transcription, followed by impaired terminal erythroid differentiation. The effect of loss on erythroid differentiation is partially rescued by overexpression of cDNA, suggesting an important role of /TAL1 regulatory axis in erythropoiesis. Mechanistically, regulates long-range chromatin interactions between Kb erythroid-specific enhancer, promoter and other regulatory elements in the locus to maintain the erythroid interaction hub. By facilitating the binding and recruitment of p300/BRG1 to the locus, promotes chromatin accessibility in the locus and activates transcription program, including subsequent epigenetic and transcriptional activation of erythroid-specific TAL1 target genes. Our study reveals a novel role for in TAL1 dependent erythropoiesis and establishes a new mode of action in transcriptional activation.