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

Yue Ren # 1 2, Yue Huo # 1 2, Weiqian Li # 1 2, Manman He 1 2, Siqi Liu 1 2, Jiabin Yang 1 2, Hongmei Zhao 2 3, Lingjie Xu 4, Yuehong Guo 1 2, Yanmin Si 1 2, Hualu Zhao 1 2, Shuan Rao 5, Jing Wang 2 3, Yanni Ma 1 2, Xiaoshuang Wang 6 7, Jia Yu 8 9 10, Fang Wang 11 12

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Genome Biol.2021 Oct 14;22(1):290. doi: 10.1186/s13059-021-02508-7.

PMID: 34649616

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Abstract

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 potentials 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.