Genetic landscape of open chromatin in yeast

PLoS Genet. 2013;9(2):e1003229. doi: 10.1371/journal.pgen.1003229. Epub 2013 Feb 7.

Abstract

Chromatin regulation underlies a variety of DNA metabolism processes, including transcription, recombination, repair, and replication. To perform a quantitative genetic analysis of chromatin accessibility, we obtained open chromatin profiles across 96 genetically different yeast strains by FAIRE (formaldehyde-assisted isolation of regulatory elements) assay followed by sequencing. While 5∼10% of open chromatin region (OCRs) were significantly affected by variations in their underlying DNA sequences, subtelomeric areas as well as gene-rich and gene-poor regions displayed high levels of sequence-independent variation. We performed quantitative trait loci (QTL) mapping using the FAIRE signal for each OCR as a quantitative trait. While individual OCRs were associated with a handful of specific genetic markers, gene expression levels were associated with many regulatory loci. We found multi-target trans-loci responsible for a very large number of OCRs, which seemed to reflect the widespread influence of certain chromatin regulators. Such regulatory hotspots were enriched for known regulatory functions, such as recombinational DNA repair, telomere replication, and general transcription control. The OCRs associated with these multi-target trans-loci coincided with recombination hotspots, telomeres, and gene-rich regions according to the function of the associated regulators. Our findings provide a global quantitative picture of the genetic architecture of chromatin regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Chromatin* / genetics
  • Chromatin* / metabolism
  • Chromosome Mapping
  • Gene Expression Regulation, Fungal
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Quantitative Trait Loci / genetics*
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Telomere / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Chromatin
  • Transcription Factors

Associated data

  • GEO/GSE33466

Grant support

This work was supported by a grant from the KRIBB Research Initiative Program and by a grant from the National Research Foundation of Korea (2012019094). GKB and JKC were supported by the Agency for Science, Technology, and Research (A*STAR) of Singapore. JKC is a recipient of the TJ Park Science Fellowship. Computing facilities were supported by the CHUNG Moon Soul Center of KAIST and a grant from the National Research Foundation of Korea (2009-0086964). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.