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HSB-1 inhibition and HSF-1 overexpression trigger overlapping transcriptional changes to promote longevity in Caenorhabditis elegans

Surojit Sural, View ORCID ProfileTzu-Chiao Lu, Seung Ah Jung, View ORCID ProfileAo-Lin Hsu
doi: https://doi.org/10.1101/535864
Surojit Sural
University of Michigan Medical School;
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Tzu-Chiao Lu
China Medical University;
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Seung Ah Jung
University of Michigan
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Ao-Lin Hsu
University of Michigan Medical School;
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  • For correspondence: aolinhsu@umich.edu
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Abstract

Heat shock factor 1 (HSF-1) is a component of the heat shock response pathway that is induced by cytoplasmic proteotoxic stress. In addition to its role in stress response, HSF-1 also acts as a key regulator of the rate of organismal aging. Overexpression of HSF-1 promotes longevity in C. elegans via mechanisms that remain less understood. Moreover, genetic ablation of a negative regulator of HSF-1, termed as heat shock factor binding protein 1 (HSB-1), results in hsf-1-dependent life span extension in animals. Here we show that in the absence of HSB-1, HSF-1 acquires increased DNA binding activity to its genomic target sequence. Using RNA-Seq to compare the gene expression profiles of the hsb-1 mutant and hsf-1 overexpression strains, we found that while more than 1,500 transcripts show ≥1.5-fold upregulation due to HSF-1 overexpression, HSB-1 inhibition alters the expression of less than 500 genes in C. elegans. Roughly half of the differentially regulated transcripts in the hsb-1 mutant have altered expression also in hsf-1 overexpressing animals, with a strongly correlated fold-expression pattern between the two strains. In addition, genes that are upregulated via both HSB-1 inhibition and HSF-1 overexpression include numerous DAF-16 targets that have known functions in longevity regulation. This study identifies how HSB-1 acts as a specific regulator of the transactivation potential of HSF-1 in non-stressed conditions, thus providing a detailed understanding of the role of HSB-1/HSF-1 signaling pathway in transcriptional regulation and longevity in C. elegans.

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Posted January 30, 2019.
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HSB-1 inhibition and HSF-1 overexpression trigger overlapping transcriptional changes to promote longevity in Caenorhabditis elegans
Surojit Sural, Tzu-Chiao Lu, Seung Ah Jung, Ao-Lin Hsu
bioRxiv 535864; doi: https://doi.org/10.1101/535864
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HSB-1 inhibition and HSF-1 overexpression trigger overlapping transcriptional changes to promote longevity in Caenorhabditis elegans
Surojit Sural, Tzu-Chiao Lu, Seung Ah Jung, Ao-Lin Hsu
bioRxiv 535864; doi: https://doi.org/10.1101/535864

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