Epigenetic modulation via the C-terminal tail of H2A.Z
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.
Authors
- Juan Ausió (ORCID: https://orcid.org/0000-0002-9674-6717)
- Masayuki Kusakabe (ORCID: https://orcid.org/0000-0001-5484-0353)
- Kata Nóra Enyedi (ORCID: https://orcid.org/0000-0003-3724-5936)
- Gábor Mocsár (ORCID: https://orcid.org/0000-0003-0570-3269)
- David J. Tremethick (ORCID: https://orcid.org/0000-0001-5274-8078)
- Erfaneh Firouzi Niaki
- Ágota Csóti
- Péter P. Nánási (ORCID: https://orcid.org/0000-0003-2976-703X)
- Margit Balázs (ORCID: https://orcid.org/0000-0002-4246-2321)
- Katalin Tóth
- Masahiko Harata
- H. T. Marc Timmers (ORCID: https://orcid.org/0000-0001-7062-1417)
- Zsolt Bacsó (ORCID: https://orcid.org/0000-0001-6885-3796)
- Zsuzsanna Darula (ORCID: https://orcid.org/0000-0003-1692-7591)
- Éva Csősz (ORCID: https://orcid.org/0000-0003-4373-2175)
- György Vámosi (ORCID: https://orcid.org/0000-0002-7940-2787)
- Rosevalentine Bosire (ORCID: https://orcid.org/0000-0002-6475-2610)
- Gábor Mező (ORCID: https://orcid.org/0000-0002-7618-7954)
- Beáta Scholtz (ORCID: https://orcid.org/0000-0002-2737-5027)
- Szilárd Póliska (ORCID: https://orcid.org/0000-0002-9722-251X)
- Ibtissem Benhamza (ORCID: https://orcid.org/0009-0000-3219-5744)
- Gábor Szabó (ORCID: https://orcid.org/0000-0002-9163-3465)
- Peter Cheung
- Éva Hegedüs
- László Imre (ORCID: https://orcid.org/0000-0001-9562-6943)
Institutions
- Eötvös Loránd University (HU)
- Australian National University (AU)
- University of Debrecen (HU)
- University of Freiburg (DE)
- York University (CA)
- Tohoku University (JP)
- University of Victoria (CA)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- University Medical Center Freiburg (DE)
- Kobe University (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-24
- DOI
- https://doi.org/10.1038/s41467-024-53514-9
- Citations
- 3
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Albert-Ludwigs-Universität Freiburg
- Hungarian Scientific Research Fund
- Debreceni Egyetem
- Università degli Studi di Camerino
- Tempus Közalapítvány
- German Network for Bioinformatics Infrastructure
- Canadian Institutes of Health Research