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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.

SUBMITTER: Kuzmanov A

PROVIDER: S-EPMC3958046 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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The conserved PBAF nucleosome-remodeling complex mediates the response to stress in Caenorhabditis elegans.

Kuzmanov Aleksandra A Karina Evguenia I EI Kirienko Natalia V NV Fay David S DS

Molecular and cellular biology 20140113 6

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 su ...[more]

PMID: 24421384

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Project description:Eukaryotic chromatin architecture is affected by intrinsic histone-DNA sequence preferences, steric exclusion between nucleosome particles, formation of higher-order structures, and in vivo activity of chromatin remodeling enzymes.To disentangle sequence-dependent nucleosome positioning from the other factors, we have created two high-throughput maps of nucleosomes assembled in vitro on genomic DNA from the nematode worm Caenorhabditis elegans. A comparison of in vitro nucleosome positions with those observed in a mixed-stage, mixed-tissue population of C. elegans cells reveals that in vivo sequence preferences are modified on the genomic scale. Indeed, G/C dinucleotides are predicted to be most favorable for nucleosome formation in vitro but not in vivo. Nucleosome sequence read coverage in vivo is distinctly lower in chromosome arms than in central regions; the observed changes in apparent nucleosome sequence specificity, likely due to genome-wide chromatin remodeler activity, contribute to the formation of these megabase-scale chromatin domains. We also observe that the majority of well-positioned in vivo nucleosomes do not occupy thermodynamically favorable sequences observed in vitro. Finally, we find that exons are intrinsically more amenable to nucleosome formation compared to introns. Nucleosome occupancy of introns and exons consistently increases with G/C content in vitro but not in vivo, in agreement with our observation that G/C dinucleotide enrichment does not strongly promote in vivo nucleosome formation.Our findings highlight the importance of both sequence specificity and active nucleosome repositioning in creating large-scale chromatin domains, and the antagonistic roles of intrinsic sequence preferences and chromatin remodelers in C. elegans.Sequence read data has been deposited into Sequence Read Archive (http://www.ncbi.nlm.nih.gov/sra; accession number SRA050182). Additional data, software and computational predictions are available on the Nucleosome Explorer website (http://nucleosome.rutgers.edu).

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Dataset Information

The conserved PBAF nucleosome-remodeling complex mediates the response to stress in Caenorhabditis elegans.

Publications

The conserved PBAF nucleosome-remodeling complex mediates the response to stress in Caenorhabditis elegans.

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