Histone H3 glutathionylation in proliferating mammalian cells destabilizes nucleosomal structure

José Luis García-Giménez, Gloria Olaso, Sandra B. Hake, Clemens Bönisch, Sonja M. Wiedemann, Jelena Markovic, Francisco Dasí, Amparo Gimeno, Carme Pérez-Quilis, Òscar Palacios, Mercè Capdevila, José Viña, Federico V. Pallardó

Research output: Contribution to journalArticleResearchpeer-review

70 Citations (Scopus)


Aims: 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. Innovation: We characterize the implications of histone H3 glutathionylation in cell physiology and the modulation of core histone proteins structure affected by this modification. Conclusion: 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. Antioxid. Redox Signal. 19, 1305-1320. © 2013, Mary Ann Liebert, Inc. 2013.
Original languageEnglish
Pages (from-to)1305-1320
JournalAntioxidants and Redox Signaling
Issue number12
Publication statusPublished - 20 Oct 2013


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