Journal
GENOME BIOLOGY
Volume 22, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13059-021-02508-7
Keywords
RNA-binding proteins (RBPs); Transcriptional regulation; QKI5; Monocytic differentiation
Funding
- National Key Research and Development Program of China [2019YFA0801800, 2019YFA0111700]
- CAMS Innovation Fund for Medical Sciences [2018-I2M-1-001, 2019-I2M-2-001, 2017-I2M-3-009, 2016-I2M-3-002, 2017-I2M-1-015]
- National Natural Science Foundation of China [81530007, 31725013, 82022001, 81970103]
- Fundamental Research Funds for the Core facility [3332019001]
- CAMS [2016GH310001, 2018RC310013, 2017-I2M-BR-04]
- Medical Epigenetics Research Center, CAMS [2017PT31035]
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The study reveals that chromatin-enriched RBPs are versatile factors orchestrating gene expression in different cellular contexts, and identifies QKI5, a classic RBP regulating RNA processing, as a novel transcriptional activator 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 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.
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