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

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

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.

Keywords: Monocytic differentiation; QKI5; RNA-binding proteins (RBPs); Transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics*
  • Cell Line
  • Chemokine CXCL2
  • Chromatin / metabolism*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Monocytes / metabolism*
  • Mutation
  • Promoter Regions, Genetic
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transcriptional Activation*
  • Transcriptome

Substances

  • CXCL2 protein, human
  • Chemokine CXCL2
  • Chromatin
  • QKI protein, human
  • RNA-Binding Proteins