Phosphorylation of histone H3 Thr-45 is linked to apoptosis

Paul J. Hurd, Andrew J. Bannister, Karen Halls, Mark A. Dawson, Michiel Vermeulen, Jesper V. Olsen, Heba Ismail, Joanna Somers, Matthias Mann, Tom Owen-Hughes, Ivan Gout, Tony Kouzarides

    Research output: Contribution to journalArticle

    71 Citations (Scopus)

    Abstract

    Numerous post-translational modifications have been identified in histones. Most of these occur within the histone tails, but a few have been identified within the histone core sequences. Histone core post-translational modifications have the potential to directly modulate nucleosome structure and consequently DNA accessibility. Here, we identify threonine 45 of histone H3 (H3T45) as a site of phosphorylation in vivo. We find that phosphorylation of H3T45 (H3T45ph) increases dramatically in apoptotic cells, around the time of DNA nicking. To further explore this connection, we analyzed human neutrophil cells because they are short-lived cells that undergo apoptosis in vivo. Freshly isolated neutrophils contain very little H3T45ph, whereas cells cultured for 20 h possess significant amounts; the kinetics of H3T45ph induction closely parallel those of caspase-3 activation. Cytokine inhibition of neutrophil apoptosis leads to reduced levels of H3T45ph. We identify protein kinase C-delta as the kinase responsible for H3T45ph in vitro and in vivo. Given the nucleosomal position of H3T45, we postulate that H3T45ph induces structural change within the nucleosome to facilitate DNA nicking and/or fragmentation.

    Original languageEnglish
    Pages (from-to)16575-16583
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume284
    Issue number24
    DOIs
    Publication statusPublished - 12 Jun 2009

    Keywords

    • KINASE C-DELTA
    • NEUTROPHIL APOPTOSIS
    • LEUKEMIA-CELLS
    • LYSINE 9
    • ACTIVATION
    • RECOGNITION
    • METHYLATION
    • TRAP
    • SITE
    • HL60

    Cite this

    Hurd, P. J., Bannister, A. J., Halls, K., Dawson, M. A., Vermeulen, M., Olsen, J. V., ... Kouzarides, T. (2009). Phosphorylation of histone H3 Thr-45 is linked to apoptosis. Journal of Biological Chemistry, 284(24), 16575-16583. https://doi.org/10.1074/jbc.M109.005421
    Hurd, Paul J. ; Bannister, Andrew J. ; Halls, Karen ; Dawson, Mark A. ; Vermeulen, Michiel ; Olsen, Jesper V. ; Ismail, Heba ; Somers, Joanna ; Mann, Matthias ; Owen-Hughes, Tom ; Gout, Ivan ; Kouzarides, Tony. / Phosphorylation of histone H3 Thr-45 is linked to apoptosis. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 24. pp. 16575-16583.
    @article{5503ee9c28ad4c35914aa24eaf04e6d2,
    title = "Phosphorylation of histone H3 Thr-45 is linked to apoptosis",
    abstract = "Numerous post-translational modifications have been identified in histones. Most of these occur within the histone tails, but a few have been identified within the histone core sequences. Histone core post-translational modifications have the potential to directly modulate nucleosome structure and consequently DNA accessibility. Here, we identify threonine 45 of histone H3 (H3T45) as a site of phosphorylation in vivo. We find that phosphorylation of H3T45 (H3T45ph) increases dramatically in apoptotic cells, around the time of DNA nicking. To further explore this connection, we analyzed human neutrophil cells because they are short-lived cells that undergo apoptosis in vivo. Freshly isolated neutrophils contain very little H3T45ph, whereas cells cultured for 20 h possess significant amounts; the kinetics of H3T45ph induction closely parallel those of caspase-3 activation. Cytokine inhibition of neutrophil apoptosis leads to reduced levels of H3T45ph. We identify protein kinase C-delta as the kinase responsible for H3T45ph in vitro and in vivo. Given the nucleosomal position of H3T45, we postulate that H3T45ph induces structural change within the nucleosome to facilitate DNA nicking and/or fragmentation.",
    keywords = "KINASE C-DELTA, NEUTROPHIL APOPTOSIS, LEUKEMIA-CELLS, LYSINE 9, ACTIVATION, RECOGNITION, METHYLATION, TRAP, SITE, HL60",
    author = "Hurd, {Paul J.} and Bannister, {Andrew J.} and Karen Halls and Dawson, {Mark A.} and Michiel Vermeulen and Olsen, {Jesper V.} and Heba Ismail and Joanna Somers and Matthias Mann and Tom Owen-Hughes and Ivan Gout and Tony Kouzarides",
    year = "2009",
    month = "6",
    day = "12",
    doi = "10.1074/jbc.M109.005421",
    language = "English",
    volume = "284",
    pages = "16575--16583",
    journal = "Journal of Biological Chemistry",
    issn = "0021-9258",
    publisher = "American Society for Biochemistry and Molecular Biology",
    number = "24",

    }

    Hurd, PJ, Bannister, AJ, Halls, K, Dawson, MA, Vermeulen, M, Olsen, JV, Ismail, H, Somers, J, Mann, M, Owen-Hughes, T, Gout, I & Kouzarides, T 2009, 'Phosphorylation of histone H3 Thr-45 is linked to apoptosis', Journal of Biological Chemistry, vol. 284, no. 24, pp. 16575-16583. https://doi.org/10.1074/jbc.M109.005421

    Phosphorylation of histone H3 Thr-45 is linked to apoptosis. / Hurd, Paul J.; Bannister, Andrew J.; Halls, Karen; Dawson, Mark A.; Vermeulen, Michiel; Olsen, Jesper V.; Ismail, Heba; Somers, Joanna; Mann, Matthias; Owen-Hughes, Tom; Gout, Ivan; Kouzarides, Tony.

    In: Journal of Biological Chemistry, Vol. 284, No. 24, 12.06.2009, p. 16575-16583.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Phosphorylation of histone H3 Thr-45 is linked to apoptosis

    AU - Hurd, Paul J.

    AU - Bannister, Andrew J.

    AU - Halls, Karen

    AU - Dawson, Mark A.

    AU - Vermeulen, Michiel

    AU - Olsen, Jesper V.

    AU - Ismail, Heba

    AU - Somers, Joanna

    AU - Mann, Matthias

    AU - Owen-Hughes, Tom

    AU - Gout, Ivan

    AU - Kouzarides, Tony

    PY - 2009/6/12

    Y1 - 2009/6/12

    N2 - Numerous post-translational modifications have been identified in histones. Most of these occur within the histone tails, but a few have been identified within the histone core sequences. Histone core post-translational modifications have the potential to directly modulate nucleosome structure and consequently DNA accessibility. Here, we identify threonine 45 of histone H3 (H3T45) as a site of phosphorylation in vivo. We find that phosphorylation of H3T45 (H3T45ph) increases dramatically in apoptotic cells, around the time of DNA nicking. To further explore this connection, we analyzed human neutrophil cells because they are short-lived cells that undergo apoptosis in vivo. Freshly isolated neutrophils contain very little H3T45ph, whereas cells cultured for 20 h possess significant amounts; the kinetics of H3T45ph induction closely parallel those of caspase-3 activation. Cytokine inhibition of neutrophil apoptosis leads to reduced levels of H3T45ph. We identify protein kinase C-delta as the kinase responsible for H3T45ph in vitro and in vivo. Given the nucleosomal position of H3T45, we postulate that H3T45ph induces structural change within the nucleosome to facilitate DNA nicking and/or fragmentation.

    AB - Numerous post-translational modifications have been identified in histones. Most of these occur within the histone tails, but a few have been identified within the histone core sequences. Histone core post-translational modifications have the potential to directly modulate nucleosome structure and consequently DNA accessibility. Here, we identify threonine 45 of histone H3 (H3T45) as a site of phosphorylation in vivo. We find that phosphorylation of H3T45 (H3T45ph) increases dramatically in apoptotic cells, around the time of DNA nicking. To further explore this connection, we analyzed human neutrophil cells because they are short-lived cells that undergo apoptosis in vivo. Freshly isolated neutrophils contain very little H3T45ph, whereas cells cultured for 20 h possess significant amounts; the kinetics of H3T45ph induction closely parallel those of caspase-3 activation. Cytokine inhibition of neutrophil apoptosis leads to reduced levels of H3T45ph. We identify protein kinase C-delta as the kinase responsible for H3T45ph in vitro and in vivo. Given the nucleosomal position of H3T45, we postulate that H3T45ph induces structural change within the nucleosome to facilitate DNA nicking and/or fragmentation.

    KW - KINASE C-DELTA

    KW - NEUTROPHIL APOPTOSIS

    KW - LEUKEMIA-CELLS

    KW - LYSINE 9

    KW - ACTIVATION

    KW - RECOGNITION

    KW - METHYLATION

    KW - TRAP

    KW - SITE

    KW - HL60

    U2 - 10.1074/jbc.M109.005421

    DO - 10.1074/jbc.M109.005421

    M3 - Article

    VL - 284

    SP - 16575

    EP - 16583

    JO - Journal of Biological Chemistry

    JF - Journal of Biological Chemistry

    SN - 0021-9258

    IS - 24

    ER -

    Hurd PJ, Bannister AJ, Halls K, Dawson MA, Vermeulen M, Olsen JV et al. Phosphorylation of histone H3 Thr-45 is linked to apoptosis. Journal of Biological Chemistry. 2009 Jun 12;284(24):16575-16583. https://doi.org/10.1074/jbc.M109.005421