GSE161943
Nuclear fractionation reveals chromatin-enriched RNA binding proteins and transcriptional regulatory activity of QKI5 during monocytic differentiation
Background: Cellular RNA binding proteins (RBPs) have multiple roles in post-transcriptional control, and some are shown to bind DNA. However, the global localization and the general chromatin-binding ability of RBPs are not well-characterized and remain undefined in hematopoietic cells. Results: We first provide a full view of RBPs' distribution pattern in the nucleus and screen for chromatin-enriched RBPs (Che-RBPs) in different human cells. Subsequently, by generating ChIP-seq, CLIP-seq and RNA-seq datasets and conducting combined analysis, the transcriptional regulatory potential of certain hematopoietic Che-RBPs are predicted. From this analysis, quaking (QKI5) emerges as a potential transcriptional activator during monocytic differentiation. QKI5 is over-represented in gene promoter regions, independent of RNA or transcription factors. Furthermore, DNA-bound QKI5 activates the transcription of several critical monocytic differentiation-associated genes, including CXCL2, IL16 and PTPN6. Finally, we show that the differentiation promoting activity of QKI5 is largely dependent on CXCL2, irrespective of its RNA binding capacity. Conclusions: Our study indicates that Che-RBPs are versatile factors that orchestrate gene expression in different cellular contexts, and identifies QKI5, a classic RBP regulating RNA processing, as a novel transcriptional activator during monocytic differentiation. Overall design: ChIP-seq, RIP-seq, and RNA-seq