Nucleosomes are context-specific, H2A.Z-modulated barriers to RNA polymerase

Mol Cell. 2014 Mar 6;53(5):819-30. doi: 10.1016/j.molcel.2014.02.014.


Nucleosomes are barriers to transcription in vitro; however, their effects on RNA polymerase in vivo are unknown. Here we describe a simple and general strategy to comprehensively map the positions of elongating and arrested RNA polymerase II (RNAPII) at nucleotide resolution. We find that the entry site of the first (+1) nucleosome is a barrier to RNAPII for essentially all genes, including those undergoing regulated pausing farther upstream. In contrast to the +1 nucleosome, gene body nucleosomes are low barriers and cause RNAPII stalling both at the entry site and near the dyad axis. The extent of the +1 nucleosome barrier correlates with nucleosome occupancy but anticorrelates with enrichment of histone variant H2A.Z. Importantly, depletion of H2A.Z from a nucleosome position results in a higher barrier to RNAPII. Our results suggest that nucleosomes present significant, context-specific barriers to RNAPII in vivo that can be tuned by the incorporation of H2A.Z.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Chromatin / chemistry
  • Cytoplasm / chemistry
  • DNA-Directed RNA Polymerases / chemistry*
  • Drosophila
  • Histones / chemistry*
  • Nucleosomes / chemistry*
  • Phosphorylation
  • Promoter Regions, Genetic*
  • RNA / chemistry
  • RNA Interference
  • RNA Polymerase II / chemistry
  • Reproducibility of Results
  • Transcription, Genetic
  • Transgenes


  • Chromatin
  • Histones
  • Nucleosomes
  • RNA
  • RNA Polymerase II
  • DNA-Directed RNA Polymerases

Associated data

  • GEO/GSE49106