Phosphatase Rtr1 regulates global levels of serine 5 RNA polymerase II C-terminal domain phosphorylation and cotranscriptional histone methylation

Gerald O. Hunter, Melanie J. Fox, Whitney R. Smith-Kinnaman, Madelaine Gogol, Brian Fleharty, Amber L. Mosley

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3). Using chromatin immunoprecipitation and high-resolution microarrays, we show that RTR1 deletion results in global changes in RNAPII Ser5-P levels on genes with different lengths and transcription rates consistent with its role as a CTD phosphatase. Although Ser5-P levels increase, the overall occupancy of RNAPII either decreases or stays the same in the absence of RTR1. Additionally, the loss of Rtr1 in vivo leads to increases in H3K36me3 levels genome-wide, while total histone H3 levels remain relatively constant within coding regions. Overall, these findings suggest that Rtr1 regulates H3K36me3 levels through changes in the number of binding sites for the histone methyltransferase Set2, thereby influencing both the CTD and histone codes.

Original languageEnglish (US)
Pages (from-to)2236-2245
Number of pages10
JournalMolecular and cellular biology
Volume36
Issue number17
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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