RNA-binding protein WDR43 binds prevalently to open chromatin and promotes gene transcription

The intricate regulation of transcription underlies cellular differentiation and development. However, the general relevance of RNA-binding proteins (RBPs) in polymerase (Pol) II transcription is less understood. Here we revealed that WDR43, a novel chromatin-bound RBP, promotes transcription and is essential for self-renewal of embryonic stem cells (ESCs) and early embryonic development. WDR43 binds to promoter-associated non-coding and nascent RNAs, localizes at thousands of gene promoters and enhancers, and interacts with the Pol II transcription machinery. Recombinant WDR43 directly promotes transcription and the release of elongation factor P-TEFb in vitro. Depletion of WDR43 in ESCs leads to global defects in Pol II pause release and mRNA expression. These results demonstrate that WDR43 maintains high-level expression of pluripotency programs by modulating Pol II activity and transcription elongation. To extend these findings, we demonstrated widespread co-occupancy of open chromatin by multiple RBPs, suggesting an unforeseen role for RBPs in transcription control Expression profiling by high throughput sequencing and genome occupancy profiling by high throughput sequencing. chrTAP-seq for WDR43.