Genome-wide transcriptional regulation of the long non-coding RNA steroid receptor RNA activator in human erythroblasts

We report a novel function of the lncRNA SRA in regulation of global gene expression through direct chromatin binding in human erythroleukemia cell line K562 and in primary human proerythroblasts derived from HSCs. We demonstrate that SRA, together with CTCF, H3K4me3, and H3K27me3, occupies various genomic regions. Further, SRA facilitates transcriptome-wide expression of erythroid program and expression of erythroid markers in K562 and in primary human proerythroblasts. Hence, a possible function of the lncRNA SRA during erythroid development is to promote transcription of erythroid genes and therefore erythropoiesis. RNA-seq analysis of both K562 and CD36-positive proerythroblasts was performed upon depletion of SRA using an Illumina HiSeq platform. Differentially expressed genes with at least two fold-change were subsequently identified by using DEseq. Three individual shRNA knockdown samples, which contain different siRNA targets, were used as biological replicates for the analysis.