ATAD2 mediates chromatin-bound histone chaperone turnover

Abstract ATAD2, a conserved protein which is predominantly expressed in embryonic stem (ES) cells and spermatogenic cells, emerges as a crucial regulator of chromatin dynamics. Our previous parallel studies in both ES cells and S. pombe highlighted the key role of ATAD2 in facilitating chromatin-bound histone chaperone turnover. Focusing on 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 Atad2 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’s interaction with histone chaperones and chromatin, which controls the balance between histone deposition and removal.

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Publication Details

Journal
eLife
Published
2025-09-22
DOI
https://doi.org/10.7554/elife.107582.1
Primary Topic
Protein Degradation and Inhibitors
Type
article
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article

ATAD2 mediates chromatin-bound histone chaperone turnover

Florent Chuffart, Charlyne Gard, André Verdel, Denis Puthier et al.
eLife
Protein Degradation and Inhibitors
article

ATAD2 mediates chromatin-bound histone chaperone turnover

Florent Chuffart, Charlyne Gard, André Verdel, Denis Puthier, Ekaterina Bourova-Flin, Ariadni Liakopoulou, Christophe Arnoult, Sophie Rousseaux, Fayçal Boussouar, Emeline Lambert, Sophie Barral, Saadi Khochbin, Daniel Perazza, Tao Wang
article en

Abstract

Abstract ATAD2, a conserved protein which is predominantly expressed in embryonic stem (ES) cells and spermatogenic cells, emerges as a crucial regulator of chromatin dynamics. Our previous parallel studies in both ES cells and S. pombe highlighted the key role of ATAD2 in facilitating chromatin-bound histone chaperone turnover. Focusing on 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 Atad2 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’s interaction with histone chaperones and chromatin, which controls the balance between histone deposition and removal.

eLife
Centre National de la Recherche Scientifique (FR), Inserm (FR), Aix-Marseille Université (FR), Université Grenoble Alpes (FR)
Openalex Percentile: Top 77%
Protein Degradation and Inhibitors
DOIOpen Access PDFOpenAlex
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ATAD2 mediates chromatin-bound histone chaperone turnover — Florent Chuffart, Charlyne Gard, et al. · eLife (2025) | TGRS Research Map | TGRS