Proteomic characterization of the arsenic response locus in S. cerevisiae

Epigenetics. 2019 Feb;14(2):130-145. doi: 10.1080/15592294.2019.1580110. Epub 2019 Mar 1.


Arsenic exposure is a global health problem. Millions of people encounter arsenic through contaminated drinking water, consumption, and inhalation. The arsenic response locus in budding yeast is responsible for the detoxification of arsenic and its removal from the cell. This locus constitutes a conserved pathway ranging from prokaryotes to higher eukaryotes. The goal of this study was to identify how transcription from the arsenic response locus is regulated in an arsenic dependent manner. An affinity enrichment strategy called CRISPR-Chromatin Affinity Purification with Mass Spectrometry (CRISPR-ChAP-MS) was used, which provides for the proteomic characterization of a targeted locus. CRISPR-ChAP-MS was applied to the promoter regions of the activated arsenic response locus and uncovered 40 nuclear-annotated proteins showing enrichment. Functional assays identified the histone acetyltransferase SAGA and the chromatin remodelling complex SWI/SNF to be required for activation of the locus. Furthermore, SAGA and SWI/SNF were both found to specifically organize the chromatin structure at the arsenic response locus for activation of gene transcription. This study provides the first proteomic characterization of an arsenic response locus and key insight into the mechanisms of transcriptional activation that are necessary for detoxification of arsenic from the cell.

Keywords: CRISPR; Chromatin; epigenetics; mass spectrometry; transcription; yeast.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Arsenate Reductases / genetics
  • Arsenic / pharmacology*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • CRISPR-Cas Systems
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal / drug effects
  • Membrane Transport Proteins / genetics
  • Promoter Regions, Genetic
  • Proteomics / methods*
  • Repressor Proteins / genetics
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • ACR3 protein, S cerevisiae
  • Basic-Leucine Zipper Transcription Factors
  • Membrane Transport Proteins
  • Repressor Proteins
  • SKO1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • ARR2 protein, S cerevisiae
  • Arsenate Reductases
  • Arsenic