Hematopoietic differentiation is controlled by both genetic and epigenetic regulators. Long non-coding RNAs (lncRNAs) have been demonstrated to be important for normal hematopoiesis, but their function in erythropoiesis needs to be further explored. Here, we profiled the transcriptome of 17 murine hematopoietic cell populations by deep sequencing and identified a novel lncRNA, that was highly expressed in erythroid-related progenitors and erythrocytes. For this reason, we named it lncEry. We also identified a novel lncEry isoform, which was the principal transcript and has not been reported before. Furthermore, we found that nearly 90% of lncEry molecules localized to the nucleus. Next, we performed knockdown and knockout assays to study the function of lncEry, and found that lncEry depletion impaired erythroid differentiation. RNA sequencing analysis showed that lncEry depletion decreased the expression of erythrocyte homeostasis or differentiation related genes, including globin genes, thus indicating its important role in regulating erythroid differentiation. Mechanistically, we performed RNA-pulldown assays and found that lncEry could interact with Wdr82, a component of the Set1A histone H3-Lys4 methyltransferase complex. In addition, a series of molecular assays indicated that lncEry could stabilize the localization of Set1A/Wdr82 complex to facilitate H3K4me3 on the promoter region of globin genes and participate in regulating erythropoiesis. These findings identify lncEry as an important player in the transcriptional regulation of globin genes to coordinate erythropoiesis.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.