Casein Kinase II Phosphorylation of Spt6 Enforces Transcriptional Fidelity by Maintaining Spn1-Spt6 Interaction

Spt6 is a histone chaperone that associates with RNA polymerase II and deposits nucleosomes in the wake of transcription. Although Spt6 has an essential function in nucleosome deposition, it is not known whether this function is regulated by post-translational modification. Here, we report that casein kinase II (CKII) phosphorylation of Spt6 directs nucleosome reassembly at the 5’ ends of a broad range of genes to prevent aberrant antisense transcription and enforce transcriptional directionality. Mechanistically, we show that interaction of Spt6 with Spn1 – a constitutive binding partner required for chromatin reassembly and full recruitment of Spt6 to genes is positively regulated by CKII phosphorylation of Spt6. Together, our study defines a previously unknown function for CKII phosphorylation in transcription, and further, highlights the importance of post-translational modification as a mechanism to fine-tune the functions of histone chaperones. Understanding the role of Spt6 phosphorylation by Casein kinase 2 and the role of such phosphorylation in the regulation of biological functions of Spt6