title: Histone h3 glutathionylation in proliferating mammalian cells destabilizes nucleosomal structure.
abstract: OBJECTIVE
  Here we report that chromatin, the complex and dynamic eukaryotic DNA packaging structure, is able to sense cellular redox changes. Histone H3, the only nucleosomal protein that possesses cysteine(s), can be modified by glutathione (GSH).
  
  
  RESULTS
  Using Biotin labeled glutathione ethyl ester (BioGEE) treatment of nucleosomes in vitro, we show that GSH, the most abundant antioxidant in mammals, binds to histone H3. BioGEE treatment of NIH3T3 cells indicates that glutathionylation of H3 is maximal in fast proliferating cells, correlating well with enhanced levels of H3 glutathionylation in different tumor cell lines. Furthermore, glutathionylation of H3 in vivo decreases in livers from aged SAMP8 and C57BL/6J mice. We demonstrate biochemically and by mass spectrometry that histone variants H3.2/H3.3 are glutathionylated on their cysteine residue 110. Furthermore, circular dichroism, thermal denaturation of reconstituted nucleosomes, and molecular modeling indicate that glutathionylation of histone H3 produces structural changes affecting nucleosomal stability.
  
  
  METHODS
  We characterize the implications of histone H3 glutathionylation in cell physiology and the modulation of core histone proteins structure affected by this modification.
  
  
  CONCLUSIONS
  Histone H3 senses cellular redox changes through glutathionylation of Cys, which increases during cell proliferation and decreases during aging. Glutathionylation of histone H3 affects nucleosome stability structure leading to a more open chromatin structure.
authors.affiliation: 1 CIBERER, Biomedical Network Research Center for Rare Diseases , Valencia, Spain .
authors.forename: José Luis
authors.initials: JL
authors.lastname: García-Giménez
authors.forename: Gloria
authors.initials: G
authors.lastname: Òlaso
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Hake
authors.forename: Clemens
authors.initials: C
authors.lastname: Bönisch
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Wiedemann
authors.forename: Jelena
authors.initials: J
authors.lastname: Markovic
authors.forename: Francisco
authors.initials: F
authors.lastname: Dasí
authors.forename: Amparo
authors.initials: A
authors.lastname: Gimeno
authors.forename: Carme
authors.initials: C
authors.lastname: Pérez-Quilis
authors.forename: Oscar
authors.initials: O
authors.lastname: Palacios
authors.forename: Mercè
authors.initials: M
authors.lastname: Capdevila
authors.forename: José
authors.initials: J
authors.lastname: Viña
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003545:Cysteine / Q000737:chemistry; D005260:Female; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D026422:S-Nitrosoglutathione / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D026422:S-Nitrosoglutathione; D003545:Cysteine
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