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. 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. 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.

中文翻译：

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全球筛选鉴定了单核细胞分化过程中富含染色质的 RNA 结合蛋白和 QKI5 的转录调控活性

细胞 RNA 结合蛋白 (RBP) 在转录后控制中具有多种作用，其中一些被证明可以结合 DNA。然而，RBP 的全局定位和一般染色质结合能力没有得到很好的表征，并且在造血细胞中仍未确定。我们首先提供了 RBP 在细胞核中分布模式的完整视图，并筛选了不同人类细胞中富含染色质的 RBP (Che-RBP)。随后，通过生成 ChIP-seq、CLIP-seq 和 RNA-seq 数据集并进行组合分析，预测某些造血 Che-RBP 的转录调控潜力。根据该分析，quaking (QKI5) 在单核细胞分化过程中作为潜在的转录激活因子出现。QKI5 在基因启动子区域中过度表达，与 RNA 或转录因子无关。此外，DNA 结合的 QKI5 激活几个关键的单核细胞分化相关基因的转录，包括 CXCL2、IL16 和 PTPN6。最后，我们表明 QKI5 的分化促进活性很大程度上依赖于 CXCL2，无论其 RNA 结合能力如何。我们的研究表明，Che-RBPs 是在不同细胞环境中协调基因表达的多功能因子，并将 QKI5（一种经典的 RBP 调节 RNA 加工）鉴定为单核细胞分化过程中的新型转录激活剂。