Analysis demonstrates ATAD2 impacts h3.3 localization and gene transcription during spermatogenesis, suggesting its vital role in chromatin regulation.
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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Liakopoulou et al. (2025) studied this question.
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