The prefoldin complex regulates chromatin dynamics during transcription elongation

PLoS Genet. 2013;9(9):e1003776. doi: 10.1371/journal.pgen.1003776. Epub 2013 Sep 19.

Abstract

Transcriptional elongation requires the concerted action of several factors that allow RNA polymerase II to advance through chromatin in a highly processive manner. In order to identify novel elongation factors, we performed systematic yeast genetic screening based on the GLAM (Gene Length-dependent Accumulation of mRNA) assay, which is used to detect defects in the expression of long transcription units. Apart from well-known transcription elongation factors, we identified mutants in the prefoldin complex subunits, which were among those that caused the most dramatic phenotype. We found that prefoldin, so far involved in the cytoplasmic co-translational assembly of protein complexes, is also present in the nucleus and that a subset of its subunits are recruited to chromatin in a transcription-dependent manner. Prefoldin influences RNA polymerase II the elongation rate in vivo and plays an especially important role in the transcription elongation of long genes and those whose promoter regions contain a canonical TATA box. Finally, we found a specific functional link between prefoldin and histone dynamics after nucleosome remodeling, which is consistent with the extensive network of genetic interactions between this factor and the machinery regulating chromatin function. This study establishes the involvement of prefoldin in transcription elongation, and supports a role for this complex in cotranscriptional histone eviction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / genetics*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Fungal
  • Histones / genetics
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism
  • Mutation
  • Nucleosomes / genetics
  • Promoter Regions, Genetic
  • RNA Polymerase II / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • TATA Box / genetics
  • Transcription, Genetic*
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • Molecular Chaperones
  • Nucleosomes
  • Transcriptional Elongation Factors
  • prefoldin
  • RNA Polymerase II

Grant support

This work has been supported by the Spanish Ministry of Economy and Competitiveness (grants BFU2007-67575-C03-02, BFU-2010-21975-C03-03 to SC, FPI fellowships to MMH, and FPU fellowship to GMZ), the Regional Andalusian Government (grants P07-CVI-02623 and P08-CVI-03508), and by the European Union (Regional Development European Fund). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.