Comprehensive structural analysis of mutant nucleosomes containing lysine to glutamine (KQ) substitutions in the H3 and H4 histone-fold domains

Wakana Iwasaki, Hiroaki Tachiwana, Koichiro Kawaguchi, Takehiko Shibata, Wataru Kagawa, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Post-translational modifications (PTMs) of histones play important roles in regulating the structure and function of chromatin in eukaryotes. Although histone PTMs were considered to mainly occur at the N-terminal tails of histones, recent studies have revealed that PTMs also exist in the histone-fold domains, which are commonly shared among the core histones H2A, H2B, H3, and H4. The lysine residue is a major target for histone PTM, and the lysine to glutamine (KQ) substitution is known to mimic the acetylated states of specific histone lysine residues in vivo. Human histones H3 and H4 contain 11 lysine residues in their histone-fold domains (five for H3 and six for H4), and eight of these lysine residues are known to be targets for acetylation. In the present study, we prepared 11 mutant nucleosomes, in which each of the lysine residues of the H3 and H4 histone-fold domains was replaced by glutamine: H3 K56Q, H3 K64Q, H3 K79Q, H3 K115Q, H3 K122Q, H4 K31Q, H4 K44Q, H4 K59Q, H4 K77Q, H4 K79Q, and H4 K91Q. The crystal structures of these mutant nucleosomes were determined at 2.4-3.5 Å resolutions. Some of these amino acid substitutions altered the local protein-DNA interactions and the interactions between amino acid residues within the nucleosome. Interestingly, the C-terminal region of H2A was significantly disordered in the nucleosome containing H4 K44Q. These results provide an important structural basis for understanding how histone modifications and mutations affect chromatin structure and function.

    Original languageEnglish
    Pages (from-to)7822-7832
    Number of pages11
    JournalBiochemistry
    Volume50
    Issue number36
    DOIs
    Publication statusPublished - 2011 Sep 13

    Fingerprint

    Nucleosomes
    Glutamine
    Structural analysis
    Histones
    Lysine
    Substitution reactions
    Post Translational Protein Processing
    Chromatin
    Histone Code
    Amino Acids
    Acetylation
    Amino Acid Substitution
    Eukaryota
    Tail
    Crystal structure

    ASJC Scopus subject areas

    • Biochemistry

    Cite this

    Comprehensive structural analysis of mutant nucleosomes containing lysine to glutamine (KQ) substitutions in the H3 and H4 histone-fold domains. / Iwasaki, Wakana; Tachiwana, Hiroaki; Kawaguchi, Koichiro; Shibata, Takehiko; Kagawa, Wataru; Kurumizaka, Hitoshi.

    In: Biochemistry, Vol. 50, No. 36, 13.09.2011, p. 7822-7832.

    Research output: Contribution to journalArticle

    Iwasaki, Wakana ; Tachiwana, Hiroaki ; Kawaguchi, Koichiro ; Shibata, Takehiko ; Kagawa, Wataru ; Kurumizaka, Hitoshi. / Comprehensive structural analysis of mutant nucleosomes containing lysine to glutamine (KQ) substitutions in the H3 and H4 histone-fold domains. In: Biochemistry. 2011 ; Vol. 50, No. 36. pp. 7822-7832.
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    abstract = "Post-translational modifications (PTMs) of histones play important roles in regulating the structure and function of chromatin in eukaryotes. Although histone PTMs were considered to mainly occur at the N-terminal tails of histones, recent studies have revealed that PTMs also exist in the histone-fold domains, which are commonly shared among the core histones H2A, H2B, H3, and H4. The lysine residue is a major target for histone PTM, and the lysine to glutamine (KQ) substitution is known to mimic the acetylated states of specific histone lysine residues in vivo. Human histones H3 and H4 contain 11 lysine residues in their histone-fold domains (five for H3 and six for H4), and eight of these lysine residues are known to be targets for acetylation. In the present study, we prepared 11 mutant nucleosomes, in which each of the lysine residues of the H3 and H4 histone-fold domains was replaced by glutamine: H3 K56Q, H3 K64Q, H3 K79Q, H3 K115Q, H3 K122Q, H4 K31Q, H4 K44Q, H4 K59Q, H4 K77Q, H4 K79Q, and H4 K91Q. The crystal structures of these mutant nucleosomes were determined at 2.4-3.5 {\AA} resolutions. Some of these amino acid substitutions altered the local protein-DNA interactions and the interactions between amino acid residues within the nucleosome. Interestingly, the C-terminal region of H2A was significantly disordered in the nucleosome containing H4 K44Q. These results provide an important structural basis for understanding how histone modifications and mutations affect chromatin structure and function.",
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