biostudies-literatureUnknown16(1)Benhamza IUsing an in situ nucleosome stability assay based on salt extraction, we identified distinct stability features of H2A.Z-containing nucleosomes linked to alternative interactions of the histone variant's C-terminal tail (Imre et al., Nat. Commun., 2024). In DT40 cells expressing either full-length or C-terminally truncated human H2A.Z1, we show that nucleosome stability is tail-dependent also through the spectacles of intercalator sensitivity, raising the possibility that the tail may bind to DNA in a superhelicity-dependent fashion. Supporting this, fluorescence correlation spectroscopy detected binding of a fluorescent H2A.Z-tail nonapeptide to supercoiled-but not relaxed-plasmid DNA, while a scrambled peptide showed negligible binding. The DNA topology-dependent binding of the unstructuNucleus (Austin, Tex.)2557113https://www.ebi.ac.uk/biostudies/studies/S-EPMC12427435biostudies-literatureH2A.Z-nucleosomes are stabilized by the superhelicity-dependent DNA binding of the C-terminal tail of the histone variant.PMC12427435Goda KImre LNanasi PSzabo GEnyedi KNVamosi GYu ZSen PBenhamza IfalseH2A.Z-nucleosomes are stabilized by the superhelicity-dependent DNA binding of the C-terminal tail of the histone variant.Using an in situ nucleosome stability assay based on salt extraction, we identified distinct stability features of H2A.Z-containing nucleosomes linked to alternative interactions of the histone variant's C-terminal tail (Imre et al., Nat. Commun., 2024). In DT40 cells expressing either full-length or C-terminally truncated human H2A.Z1, we show that nucleosome stability is tail-dependent also through the spectacles of intercalator sensitivity, raising the possibility that the tail may bind to DNA in a superhelicity-dependent fashion. Supporting this, fluorescence correlation spectroscopy detected binding of a fluorescent H2A.Z-tail nonapeptide to supercoiled-but not relaxed-plasmid DNA, while a scrambled peptide showed negligible binding. The DNA topology-dependent binding of the unstructu2025-01-01T00:00:00Z2025 Dec2026-06-01T12:04:37.943Z2026-04-08T12:01:59.623ZS-EPMC124274354092631510.1080/19491034.2025.2557113