RNA Pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD Phosphorylation, and Transcriptional Direction

• Published in: Molecular cell 2017-05, Vol.66 (4), p.546-557.e3
• Main Authors: Fong, Nova, Saldi, Tassa, Sheridan, Ryan M., Cortazar, Michael A., Bentley, David L.
• Format: Article
• Language: English
• Subjects: antisense transcription; bidirectional transcription; Chromatin - enzymology; Chromatin - genetics; Chromatin Assembly and Disassembly; DNA, Fungal - genetics; DNA, Fungal - metabolism; Gene Expression Regulation, Fungal; H3K4me2; HEK293 Cells; histone methylation; Humans; K3K36me3; kinetic coupling; Mutation; Phosphorylation; pol II CTD S2 phosphorylation; pol II dynamics; Protein Domains; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Time Factors; transcription elongation rate; Transcription, Genetic
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2017.04.016

Eukaryotic genes are marked by conserved post-translational modifications on the RNA pol II C-terminal domain (CTD) and the chromatin template. How the 5′-3′ profiles of these marks are established is poorly understood. Using pol II mutants in human cells, we found that slow transcription repositioned specific co-transcriptionally deposited chromatin modifications; histone H3 lysine 36 trimethyl (H3K36me3) shifted within genes toward 5′ ends, and histone H3 lysine 4 dimethyl (H3K4me2) extended farther upstream of start sites. Slow transcription also evoked a hyperphosphorylation of CTD Ser2 residues at 5′ ends of genes that is conserved in yeast. We propose a “dwell time in the target zone” model to explain the effects of transcriptional dynamics on the establishment of co-transcriptionally deposited protein modifications. Promoter-proximal Ser2 phosphorylation is associated with a longer pol II dwell time at start sites and reduced transcriptional polarity because of strongly enhanced divergent antisense transcription at promoters. These results demonstrate that pol II dynamics help govern the decision between sense and divergent antisense transcription. [Display omitted] •Slow pol II shifts H3K36 methylation toward 5′ ends of genes•Slow pol II dynamics cause pol II CTD Ser2 hyperphosphorylation at 5′ ends•Ser2 phosphorylation at 5′ ends correlates with increased divergent transcription•“Dwell-time in the target zone” model for co-transcriptional protein modification Transcribed genes are marked by conserved 5′-3′ profiles of post-translational modifications on RNA polymerase II and chromatin. Fong et al. show that pol II speed helps fashion 5′-3′ profiles of CTD Ser2-PO4 and histone H3 K4/K36 methylation and influences the polarity of transcription at bidirectional promoters.