DAXX governs the silencing of LINE1 during spermatogenesis in mice

The suppression of transposable elements in the germline is critical for safeguarding fertility. Here we identified that DAXX (death-associated protein 6), a potent transcription repressor and an H3.3 chaperone, was indispensable for silencing of transposable elements during spermatogenesis. Daxx germline conditional knockout mice exhibited delayed meiotic progression, spermiogenesis defects, and an age-dependent decline in fertility. The ablation of DAXX led to activation of evolutionarily young long interspersed nuclear element-1 (LINE1) and endogenous retrovirus (ERV) subfamilies. Further mechanistic study revealed that DAXX participated in the repression of young LINE1s by regulating H3K9me3 enrichment and maintaining DNA methylation. In summary, this study identifies DAXX as a previously unknown regulator of spermatogenesis and demonstrates that it functions as an epigenetic regulator to silence young LINE1s.