Casein Kinase II Phosphorylation of Spt6 Enforces Transcriptional Fidelity by Maintaining Spn1-Spt6 Interaction
Raghuvar Dronamraju,
Jenny L. Kerschner,
Sarah A. Peck,
Austin J. Hepperla,
Alexander T. Adams,
Katlyn D. Hughes,
Sadia Aslam,
Andrew R. Yoblinski,
Ian J. Davis,
Amber L. Mosley,
Brian D. Strahl
Affiliations
Raghuvar Dronamraju
Department of Biochemistry & Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Jenny L. Kerschner
Department of Biochemistry & Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Sarah A. Peck
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Austin J. Hepperla
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Alexander T. Adams
Department of Biochemistry & Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Katlyn D. Hughes
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Sadia Aslam
Department of Biochemistry & Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Andrew R. Yoblinski
Department of Biochemistry & Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Ian J. Davis
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Amber L. Mosley
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Brian D. Strahl
Department of Biochemistry & Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Corresponding author
Summary: 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 influenced by post-translational modification. Here, we report that casein kinase II (CKII) phosphorylation of Spt6 is required for nucleosome occupancy at the 5′ ends of genes to prevent aberrant antisense transcription and enforce transcriptional directionality. Mechanistically, we show that CKII phosphorylation of Spt6 promotes the interaction of Spt6 with Spn1, a binding partner required for chromatin reassembly and full recruitment of Spt6 to genes. Our study defines a function for CKII phosphorylation in transcription and highlights the importance of post-translational modification in histone chaperone function. : Dronamraju et al. show that the N terminus of Spt6 is phosphorylated by casein kinase II, which is required for proper Spt6-Spn1 interaction. CKII phosphorylation of Spt6 is pivotal to maintain nucleosome occupancy at the 5′ ends of genes, suppression of antisense transcription from the 5′ ends, and resistance to genotoxic agents. Keywords: Spt6, CKII, Spn1, nucleosome occupancy, SILAC
