Genome-Wide Transcriptional Regulation of the Long Non-coding RNA Steroid Receptor RNA Activator in Human Erythroblasts

Erythropoiesis of human hematopoietic stem cells (HSCs) maintains generation of red blood cells throughout life. However, little is known how human erythropoiesis is regulated by long non-coding RNAs (lncRNAs). By using ChIRP-seq, we report here that the lncRNA steroid receptor RNA activator (SRA) occupies chromatin, and co-localizes with CTCF, H3K4me3, and H3K27me3 genome-wide in human erythroblast cell line K562. CTCF binding sites that are also occupied by SRA are enriched for either H3K4me3 or H3K27me3. Transcriptome-wide analyses reveal that SRA facilitates expression of erythroid-associated genes, while repressing leukocyte-associated genes in both K562 and CD36-positive primary human proerythroblasts derived from HSCs. We find that SRA-regulated genes are enriched by both CTCF and SRA bindings. Further, silencing of SRA decreases expression of the erythroid-specific markers TFRC and GYPA, and down-regulates expression of globin genes in both K562 and human proerythroblast cells. Taken together, our findings establish that the lncRNA SRA occupies chromatin, and promotes transcription of erythroid genes, therefore facilitating human erythroid transcriptional program.