Promoter nucleosome dynamics regulated by signalling through the CTD code

Elife. 2015 Jun 22;4:e09008. doi: 10.7554/eLife.09008.

Abstract

The phosphorylation of the RNA polymerase II C-terminal domain (CTD) plays a key role in delineating transcribed regions within chromatin by recruiting histone methylases and deacetylases. Using genome-wide nucleosome mapping, we show that CTD S2 phosphorylation controls nucleosome dynamics in the promoter of a subset of 324 genes, including the regulators of cell differentiation ste11 and metabolic adaptation inv1. Mechanistic studies on these genes indicate that during gene activation a local increase of phospho-S2 CTD nearby the promoter impairs the phospho-S5 CTD-dependent recruitment of Set1 and the subsequent recruitment of specific HDACs, which leads to nucleosome depletion and efficient transcription. The early increase of phospho-S2 results from the phosphorylation of the CTD S2 kinase Lsk1 by MAP kinase in response to cellular signalling. The artificial tethering of the Lsk1 kinase at the ste11 promoter is sufficient to activate transcription. Therefore, signalling through the CTD code regulates promoter nucleosomes dynamics.

Keywords: HDAC; MAP kinase; RNA polymerase; S. pombe; Set1; chromatin; chromosomes; genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Molecular Sequence Data
  • Nucleosomes / metabolism*
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational*
  • RNA Polymerase II / metabolism*
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Sequence Analysis, DNA
  • Signal Transduction
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Nucleosomes
  • RNA Polymerase II

Associated data

  • GEO/GSE59768

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.