A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation

Background: Cellular RNA binding proteins (RBPs) have multiple roles in post-transcriptional control, and some have been shown to bind DNA. However, the global localization and the general chromatin-binding ability of RBPs have not been well-characterized and remain undefined in hematopoietic cells. Results: We first provided a full view of RBPs’ distribution pattern in nucleus and screened 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 were predicted and from which quaking (QKI5) emerged as a potential transcriptional activator during monocytic differentiation. QKI5 was over-represented in gene promoter regions, independent of RNA or transcription factors. Furthermore, promoter-occupied QKI5 activated the transcription of several critical monocytic differentiation-associated genes, including CXCL2, IL16 and PTPN6. Finally, we showed 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. H3K4me3 and Pol II ChIP-seq with input in untreated THP-1 cells and QKI5 knockdown THP-1 cells. QKI5 CLIP-seq with input in untreated THP-1 cells and QKI5 knockdown THP-1 cells. Please note that each processed data was generated from both replicates and is linked to the corresponding *rep1 records.