Proteotoxic stress reprograms the chromatin landscape of SUMO modification

Anne Seifert, Pieta Schofield, Geoffrey Barton, Ronald Hay (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    30 Citations (Scopus)
    125 Downloads (Pure)

    Abstract

    The small ubiquitin-like modifier 2 (SUMO-2) is required for survival when cells are exposed to treatments that induce proteotoxic stress by causing the accumulation of misfolded proteins. Exposure of cells to heat shock or other forms of proteotoxic stress induces the conjugation of SUMO-2 to proteins in the nucleus. Here, we investigated the chromatin landscape of SUMO-2 modifications in response to heat stress. Through chromatin immunoprecipitation assays coupled to high-throughput DNA sequencing and with mRNA sequencing, we showed that in response to heat shock, SUMO-2 accumulated at nucleosome-depleted, active DNA-regulatory elements, which represented binding sites for large protein complexes and were predominantly associated with active genes. However, SUMO did not act as a direct transcriptional repressor or activator of these genes during heat shock. Instead, integration of our results with published proteomics data on heat shock–induced SUMO-2 substrates supports a model in which the conjugation of SUMO-2 to proteins acts as an acute stress response that is required for the stability of protein complexes involved in gene expression and posttranscriptional modification of mRNA. We showed that the conjugation of SUMO-2 to chromatin-associated proteins is an integral component of the proteotoxic stress response, and propose that SUMO-2 fulfills its essential role in cell survival by contributing to the maintenance of protein complex homeostasis.
    Original languageEnglish
    Pages (from-to)rs7
    Number of pages14
    JournalScience Signaling
    Volume8
    Issue number384
    DOIs
    Publication statusPublished - 7 Jul 2015

    Fingerprint

    Ubiquitin
    Chromatin
    Proteins
    Heat-Shock Response
    Hot Temperature
    Shock
    Cell Survival
    Genes
    High-Throughput Nucleotide Sequencing
    Messenger RNA
    Nucleosomes
    Protein Stability
    Chromatin Immunoprecipitation
    DNA
    Gene expression
    Proteomics
    Assays
    Homeostasis
    Binding Sites
    Cells

    Cite this

    @article{0ce821c6e1d846eb94743483af346678,
    title = "Proteotoxic stress reprograms the chromatin landscape of SUMO modification",
    abstract = "The small ubiquitin-like modifier 2 (SUMO-2) is required for survival when cells are exposed to treatments that induce proteotoxic stress by causing the accumulation of misfolded proteins. Exposure of cells to heat shock or other forms of proteotoxic stress induces the conjugation of SUMO-2 to proteins in the nucleus. Here, we investigated the chromatin landscape of SUMO-2 modifications in response to heat stress. Through chromatin immunoprecipitation assays coupled to high-throughput DNA sequencing and with mRNA sequencing, we showed that in response to heat shock, SUMO-2 accumulated at nucleosome-depleted, active DNA-regulatory elements, which represented binding sites for large protein complexes and were predominantly associated with active genes. However, SUMO did not act as a direct transcriptional repressor or activator of these genes during heat shock. Instead, integration of our results with published proteomics data on heat shock–induced SUMO-2 substrates supports a model in which the conjugation of SUMO-2 to proteins acts as an acute stress response that is required for the stability of protein complexes involved in gene expression and posttranscriptional modification of mRNA. We showed that the conjugation of SUMO-2 to chromatin-associated proteins is an integral component of the proteotoxic stress response, and propose that SUMO-2 fulfills its essential role in cell survival by contributing to the maintenance of protein complex homeostasis.",
    author = "Anne Seifert and Pieta Schofield and Geoffrey Barton and Ronald Hay",
    year = "2015",
    month = "7",
    day = "7",
    doi = "10.1126/scisignal.aaa2213",
    language = "English",
    volume = "8",
    pages = "rs7",
    journal = "Science Signaling",
    issn = "1937-9145",
    publisher = "American Association for the Advancement of Science",
    number = "384",

    }

    Proteotoxic stress reprograms the chromatin landscape of SUMO modification. / Seifert, Anne; Schofield, Pieta; Barton, Geoffrey; Hay, Ronald (Lead / Corresponding author).

    In: Science Signaling, Vol. 8, No. 384, 07.07.2015, p. rs7.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Proteotoxic stress reprograms the chromatin landscape of SUMO modification

    AU - Seifert, Anne

    AU - Schofield, Pieta

    AU - Barton, Geoffrey

    AU - Hay, Ronald

    PY - 2015/7/7

    Y1 - 2015/7/7

    N2 - The small ubiquitin-like modifier 2 (SUMO-2) is required for survival when cells are exposed to treatments that induce proteotoxic stress by causing the accumulation of misfolded proteins. Exposure of cells to heat shock or other forms of proteotoxic stress induces the conjugation of SUMO-2 to proteins in the nucleus. Here, we investigated the chromatin landscape of SUMO-2 modifications in response to heat stress. Through chromatin immunoprecipitation assays coupled to high-throughput DNA sequencing and with mRNA sequencing, we showed that in response to heat shock, SUMO-2 accumulated at nucleosome-depleted, active DNA-regulatory elements, which represented binding sites for large protein complexes and were predominantly associated with active genes. However, SUMO did not act as a direct transcriptional repressor or activator of these genes during heat shock. Instead, integration of our results with published proteomics data on heat shock–induced SUMO-2 substrates supports a model in which the conjugation of SUMO-2 to proteins acts as an acute stress response that is required for the stability of protein complexes involved in gene expression and posttranscriptional modification of mRNA. We showed that the conjugation of SUMO-2 to chromatin-associated proteins is an integral component of the proteotoxic stress response, and propose that SUMO-2 fulfills its essential role in cell survival by contributing to the maintenance of protein complex homeostasis.

    AB - The small ubiquitin-like modifier 2 (SUMO-2) is required for survival when cells are exposed to treatments that induce proteotoxic stress by causing the accumulation of misfolded proteins. Exposure of cells to heat shock or other forms of proteotoxic stress induces the conjugation of SUMO-2 to proteins in the nucleus. Here, we investigated the chromatin landscape of SUMO-2 modifications in response to heat stress. Through chromatin immunoprecipitation assays coupled to high-throughput DNA sequencing and with mRNA sequencing, we showed that in response to heat shock, SUMO-2 accumulated at nucleosome-depleted, active DNA-regulatory elements, which represented binding sites for large protein complexes and were predominantly associated with active genes. However, SUMO did not act as a direct transcriptional repressor or activator of these genes during heat shock. Instead, integration of our results with published proteomics data on heat shock–induced SUMO-2 substrates supports a model in which the conjugation of SUMO-2 to proteins acts as an acute stress response that is required for the stability of protein complexes involved in gene expression and posttranscriptional modification of mRNA. We showed that the conjugation of SUMO-2 to chromatin-associated proteins is an integral component of the proteotoxic stress response, and propose that SUMO-2 fulfills its essential role in cell survival by contributing to the maintenance of protein complex homeostasis.

    U2 - 10.1126/scisignal.aaa2213

    DO - 10.1126/scisignal.aaa2213

    M3 - Article

    VL - 8

    SP - rs7

    JO - Science Signaling

    JF - Science Signaling

    SN - 1937-9145

    IS - 384

    ER -