Proteomic characterization of the arsenic response locus in S. cerevisiae

Kirk L. West, Stephanie D. Byrum, Samuel G. Mackintosh, Rick D. Edmondson, Sean Dixon Taverna, Alan J. Tackett

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalEpigenetics
DOIs
StatePublished - Jan 1 2019

Fingerprint

Arsenic
Proteomics
Saccharomyces cerevisiae
Clustered Regularly Interspaced Short Palindromic Repeats
Transcriptional Activation
Chromatin
Mass Spectrometry
Histone Acetyltransferases
Saccharomycetales
Chromatin Assembly and Disassembly
Nuclear Proteins
Eukaryota
Genetic Promoter Regions
Drinking Water
Inhalation
Drinking

Keywords

  • Chromatin
  • CRISPR
  • epigenetics
  • mass spectrometry
  • transcription
  • yeast

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Proteomic characterization of the arsenic response locus in S. cerevisiae. / West, Kirk L.; Byrum, Stephanie D.; Mackintosh, Samuel G.; Edmondson, Rick D.; Taverna, Sean Dixon; Tackett, Alan J.

In: Epigenetics, 01.01.2019.

Research output: Contribution to journalArticle

West, Kirk L. ; Byrum, Stephanie D. ; Mackintosh, Samuel G. ; Edmondson, Rick D. ; Taverna, Sean Dixon ; Tackett, Alan J. / Proteomic characterization of the arsenic response locus in S. cerevisiae. In: Epigenetics. 2019.
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