Epigenetic modulation via the C-terminal tail of H2A.Z

Imre, László and Nánási, Péter Pál and Benhamza, Ibtissem and Enyedi, Kata Nóra and Mocsár, Gábor and Bosire, Rosevalentine and Hegedüs, Éva and Firouzi Niaki, Erfaneh and Csóti, Ágota and Darula, Zsuzsanna and Csősz, Éva and Póliska, Szilárd and Scholtz, Beáta and Mező, Gábor and Bacsó, Zsolt and Timmers, H. T. Marc and Kusakabe, Masayuki and Balázs, Margit and Vámosi, György and Ausio, Juan and Cheung, Peter and Tóth, Katalin and Tremethick, David and Harata, Masahiko and Szabó, Gábor (2024) Epigenetic modulation via the C-terminal tail of H2A.Z. NATURE COMMUNICATIONS, 15. No. 9171. ISSN 2041-1723

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Abstract

H2A.Z-nucleosomes are present in both euchromatin and heterochromatin and it has proven difficult to interpret their disparate roles in the context of their stability features. Using an in situ assay of nucleosome stability and DT40 cells expressing engineered forms of the histone variant we show that native H2A.Z, but not C-terminally truncated H2A.Z (H2A.Z∆C), is released from nucleosomes of peripheral heterochromatin at unusually high salt concentrations. H2A.Z and H3K9me3 landscapes are reorganized in H2A.Z∆C-nuclei and overall sensitivity of chromatin to nucleases is increased. These tail-dependent differences are recapitulated upon treatment of HeLa nuclei with the H2A.Z-tail-peptide (C9), with MNase sensitivity being increased genome-wide. Fluorescence correlation spectroscopy revealed C9 binding to reconstituted nucleosomes. When introduced into live cells, C9 elicited chromatin reorganization, overall nucleosome destabilization and changes in gene expression. Thus, H2A.Z-nucleosomes influence global chromatin architecture in a tail-dependent manner, what can be modulated by introducing the tail-peptide into live cells.

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