Deimination stabilizes histone H2A/H2B dimers as revealed by electrospray ionization mass spectrometry

Shingo Shimoyama, Aritaka Nagadoi, Hiroaki Tachiwana, Michiyuki Yamada, Mamoru Sato, Hitoshi Kurumizaka, Yoshifumi Nishimura, Satoko Akashi

    Research output: Contribution to journalArticlepeer-review

    18 Citations (Scopus)

    Abstract

    Post-translational modifications of histones for reversibly changing chromosomal structures in promoter regions of genes are a prerequisite for transcriptional activation and repression of genes. Peptidylarginine deiminase 4 (PAD4), which mediates histone deimination by converting arginine residues into citrulline residues, is involved in the repression of gene transcription. However, the mechanism is still unclear. We studied the effects of deimination on the reconstituted histone H2A/H2B dimer structure by electrospray ionization mass spectrometry. Deimination of the H2A/H2B dimer by PAD4 indicated that the mass of H2A increased 2.7 Da, suggesting that two or three Arg residues of H2A were deiminated. Deimination of H2A monomer alone showed a 6.6-Da increase in mass. This indicates that about four more Arg residues of H2A are modified in the monomer state than in the H2A/H2B dimer state. Taking account of the finding that the unstructured portions in proteins are susceptible to deimination by PAD4, it is likely that H2A in the monomer state has a more flexible structure than that in the dimer state. Furthermore, analysis of the association of the H2A/H2B dimer in 2 or 4 M ammonium acetate with nano-electrospray ionization mass spectrometry showed that a modified H2A/H2B dimer was less dissociated into H2A and H2B monomers than an unmodified dimer when high voltages were applied to the sample cone. This study provides convincing evidence that PAD4 deimination stabilizes the histone H2A/H2B dimer.

    Original languageEnglish
    Pages (from-to)900-908
    Number of pages9
    JournalJournal of Mass Spectrometry
    Volume45
    Issue number8
    DOIs
    Publication statusPublished - 2010 Aug

    Keywords

    • Complex stability
    • Deimination
    • Dissociation
    • Electrospray ionization mass spectrometry
    • Histone H2A/H2B

    ASJC Scopus subject areas

    • Spectroscopy

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