ATAD2 mediates chromatin-bound histone chaperone turnover.

Liakopoulou, Ariadni; Boussouar, Fayçal; Perazza, Daniel; Barral, Sophie; Lambert, Emeline; Wang, Tao; Chuffart, Florent; Bourova-Flin, Ekaterina et al. · Elife · 2026

basic_science · Level V

Where this comes from

Abstract

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.

Medical subject headings