Novel ZC3H4-WDR82-CK2 complex phosphorylates SPT5 and represses aberrant transcription

Abstract

CK2 is an essential protein kinase that mediates various cellular processes, which particularly plays a crucial role in chromatin modulation and transcription elongation. However, it is still poorly understood how CK2 is localized to chromatin and how it regulates transcription. In this study, we used immunoprecipitation and mass spectrometry to identify a novel multimeric complex composed of ZC3H4, WDR82 and CK2α/β (denoted as ZWC complex). Further characterization revealed a stable multimeric CK2 kinase complex that contains CK2α, CK2β, WDR82 and ZC3H4 as a binding platform. WDR82 and ZC3H4 recognize Ser5 phosphorylated RNAPII CTD, and all subunits are co-localized in the transcription start sites of active genes. We also showed that this novel CK2 complex phosphorylates multiple residues in the N-terminus of SPT5, and that ZC3H4 is crucial for CK2-mediated SPT5 phosphorylation. Mutation of the CK2 phosphorylation site in SPT5 or knockdown of ZC3H4 leads to the increase of aberrant antisense transcription near TSSs. Taken together, our data indicate that ZC3H4 and WDR82 form a complex with CK2 and play an important role in CK2 function and localization, and that ZWC complex-mediated SPT5 phosphorylation prevents aberrant antisense transcription.