ATAD2 mediates chromatin-bound histone chaperone turnover
ATAD2, a conserved protein which is predominantly expressed in embryonic stem (ES) cells and spermatogenic cells, emerges as a crucial regulator of chromatin plasticity. Our previous parallel studies conducted in both ES cells and <i>S. pombe</i> highlighted the fundamental role of ATAD2 in facilitating chromatin-bound histone chaperone turnover. Focusing on mouse spermatogenesis, we demonstrate here that ATAD2 regulates the HIRA-dependent localization of H3.3 on the genome and influences H3.3-mediated gene transcription. Moreover, by modulating histone eviction and the assembly of protamines, ATAD2 ensures proper chromatin condensation and genome packaging in mature sperm. Disruption of <i>Atad2</i> function in mice leads to abnormal genome organization in mature spermatozoa. Together, these findings establish a previously overlooked level of chromatin dynamic regulation, governed by ATAD2-controlled histone chaperones binding to chromatin, which defines the balance between histone deposition and removal.
Authors
- Florent Chuffart (ORCID: https://orcid.org/0000-0001-6064-5183)
- Charlyne Gard (ORCID: https://orcid.org/0009-0004-1608-0110)
- André Verdel (ORCID: https://orcid.org/0000-0001-6048-3794)
- Denis Puthier (ORCID: https://orcid.org/0000-0002-7240-5280)
- Ekaterina Bourova-Flin (ORCID: https://orcid.org/0000-0002-5673-9045)
- Ariadni Liakopoulou
- Christophe Arnoult (ORCID: https://orcid.org/0000-0002-3753-5901)
- Sophie Rousseaux (ORCID: https://orcid.org/0000-0001-5246-5350)
- Fayçal Boussouar (ORCID: https://orcid.org/0000-0003-4529-4893)
- Emeline Lambert
- Sophie Barral (ORCID: https://orcid.org/0000-0001-9915-6096)
- Saadi Khochbin (ORCID: https://orcid.org/0000-0002-0455-0857)
- Daniel Perazza (ORCID: https://orcid.org/0000-0002-7703-4984)
- Tao Wang (ORCID: https://orcid.org/0000-0002-5178-6969)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Aix-Marseille Université (FR)
- Université Grenoble Alpes (FR)
Publication Details
- Journal
- eLife
- Published
- 2025-09-22
- DOI
- https://doi.org/10.7554/elife.107582
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Aix-Marseille Université
- Infrastructures en Biologie Santé et Agronomie
- Alliance Nationale pour les Sciences de la Vie et de la Santé
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale