H2A.Z-nucleosomes are stabilized by the superhelicity-dependent DNA binding of the C-terminal tail of the histone variant.

Abstract

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 unstructured H2A.Z C-terminus, by affecting nucleosome stability, may be of functional significance in various roles of the histone variant, demonstrating the strong interplay between DNA topology and nucleosome stability and exemplifying how it may be exploited by the cell for regulatory purposes.