The Conserved PBAF Nucleosome-Remodeling Complex Mediates the Response to Stress in Caenorhabditis elegans

Abstract

To adapt to stress, cells must undergo major changes in their gene expression profiles. We have previously described a largely uncharacterized stress response pathway in Caenorhabditis elegans that acts through an evolutionarily conserved motif, termed ESRE, for ethanol and stress response element. We characterize here the requirements for ESRE gene expression and show that the ESRE network is regulated by a conserved SWI/SNF family nucleosome remodeling complex termed PBAF. Depletion of PBAF subunits SWSN-7/BAF200 and PBRM-1/BAF180 results in decreased expression of ESRE genes and increased sensitivity to thermal stress. When overexpressed, SWSN-7/BAF200 and PBRM-1/BAF180 led to increased ESRE transcription, enhanced thermotolerance, and induction of a nuclear ESRE-binding activity. Our data support a model in which PBAF is recruited by an ESRE-binding protein to genomic ESRE sites. We also show that the closely related SWI/SNF complex, BAF, which regulates stress induction through DAF-16/FOXO, does not contribute to ESRE gene expression or bind directly to ESRE sites. To our knowledge, this is the first report demonstrating direct and specific regulation of a stress response network by the PBAF nucleosome-remodeling complex in vivo in metazoa. In addition, we show that PBAF cooperates with the histone demethylase, JMJC-1/NO66, to promote expression of ESRE genes following stress.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01502-13.

ACKNOWLEDGMENTS

We thank Amy Fluet for editing, Harry Jarrett for technical advice and experimental assistance, and Junho Lee for reagents. We thank the Caenorhabditis elegans Genetics Center and the North American and Japanese (National BioResource Project) gene knockout consortiums for strains. We also thank Valerie Reinke and Michelle Kudron for advice on ChIP analysis.

This study was supported by National Institutes of Health grant R01 GM066868-06 and by INBRE (P20 GM103432).