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

László Imre, Péter Nánási, Ibtissem Benhamza, Kata Nóra Enyedi, Gábor Mocsár, Rosevalentine Bosire, Éva Hegedüs, Erfaneh Firouzi Niaki, Ágota Csóti, Zsuzsanna Darula, Éva Csősz, Szilárd Póliska, Beáta Scholtz, Gábor Mező, Zsolt Bacsó, H. T. Marc Timmers, Masayuki Kusakabe, Margit Balázs, György Vámosi, Juan Ausio, Peter Cheung, Katalin Tóth, David Tremethick, Masahiko Harata and Gábor Szabó ()
Additional contact information
László Imre: Faculty of Medicine, University of Debrecen
Péter Nánási: Faculty of Medicine, University of Debrecen
Ibtissem Benhamza: Faculty of Medicine, University of Debrecen
Kata Nóra Enyedi: Institute of Chemistry, Eötvös Loránd University
Gábor Mocsár: Department of Biophysics and Cell Biology, University of Debrecen, Faculty of Medicine
Rosevalentine Bosire: Faculty of Medicine, University of Debrecen
Éva Hegedüs: Faculty of Medicine, University of Debrecen
Erfaneh Firouzi Niaki: Faculty of Medicine, University of Debrecen
Ágota Csóti: Faculty of Medicine, University of Debrecen
Zsuzsanna Darula: Hungarian Centre of Excellence for Molecular Medicine
Éva Csősz: Faculty of Medicine, University of Debrecen
Szilárd Póliska: Faculty of Medicine, University of Debrecen
Beáta Scholtz: Faculty of Medicine, University of Debrecen
Gábor Mező: Institute of Chemistry, Eötvös Loránd University
Zsolt Bacsó: Faculty of Medicine, University of Debrecen
H. T. Marc Timmers: Medical Center-University of Freiburg
Masayuki Kusakabe: Kobe University
Margit Balázs: Faculty of Medicine, University of Debrecen
György Vámosi: Faculty of Medicine, University of Debrecen
Juan Ausio: University of Victoria
Peter Cheung: York University
Katalin Tóth: Faculty of Medicine, University of Debrecen
David Tremethick: The Australian National University
Masahiko Harata: Graduate School of Agricultural Science, Tohoku University
Gábor Szabó: Faculty of Medicine, University of Debrecen

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53514-9

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