A high-throughput ChIP-Seq for large-scale chromatin studies

Mol Syst Biol. 2015 Jan 12;11(1):777. doi: 10.15252/msb.20145776.


We present a modified approach of chromatin immuno-precipitation followed by sequencing (ChIP-Seq), which relies on the direct ligation of molecular barcodes to chromatin fragments, thereby permitting experimental scale-up. With Bar-ChIP now enabling the concurrent profiling of multiple DNA-protein interactions, we report the simultaneous generation of 90 ChIP-Seq datasets without any robotic instrumentation. We demonstrate that application of Bar-ChIP to a panel of Saccharomyces cerevisiae chromatin-associated mutants provides a rapid and accurate genome-wide overview of their chromatin status. Additionally, we validate the utility of this technology to derive novel biological insights by identifying a role for the Rpd3S complex in maintaining H3K14 hypo-acetylation in gene bodies. We also report an association between the presence of intragenic H3K4 tri-methylation and the emergence of cryptic transcription in a Set2 mutant. Finally, we uncover a crosstalk between H3K14 acetylation and H3K4 methylation in this mutant. These results show that Bar-ChIP enables biological discovery through rapid chromatin profiling at single-nucleosome resolution for various conditions and protein modifications at once.

Keywords: ChIP‐Seq; chromatin; high‐throughput; histone marks; histone methyltransferase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Chromatin / chemistry
  • Chromatin / genetics*
  • Chromatin Immunoprecipitation / methods*
  • DNA, Fungal / genetics
  • Databases, Genetic
  • Gene Expression Profiling
  • Genetic Association Studies
  • Genetic Markers
  • High-Throughput Nucleotide Sequencing / methods*
  • Histones / genetics
  • Histones / metabolism
  • Methylation
  • Nucleosomes
  • Reproducibility of Results
  • Saccharomyces cerevisiae / genetics
  • Sequence Alignment
  • Sequence Analysis, DNA


  • Chromatin
  • DNA, Fungal
  • Genetic Markers
  • Histones
  • Nucleosomes