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

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    75 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

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