Proteomic Analysis of an Arsenic Response Locus

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 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 that provides for the proteomic characterization of a given locus. CRISPR-ChAP-MS was applied to the arsenic response locus and uncovered 40 nuclear-annotated proteins showing enrichment. Functional assays, identified the histone acetyltransferase activity of SAGA and the ATPase chromatin remodeling activity of 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 mechanism of transcriptional activation that is necessary for detoxification of arsenic from the cell.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Stephanie Byrum  

LAB HEAD: Alan J. Tackett

PROVIDER: PXD009902 | Pride | 2020-05-07

REPOSITORIES: Pride