DAXX governs the silencing of LINE1 during spermatogenesis in mice [BiSulfite-seq]

The suppression of transposable elements in germline is critical for safeguarding fertility. Here we identify that the DAXX, a potent transcription repressor and an H3.3 chaperone, is indispensable for transposable elements silencing during spermatogenesis. Male mice with conditional knockout of Daxx in germ cells mediated by Ddx4-cre display delayed meiotic progression, deformed and reduced production of sperms, and an age-dependent decline in fertility. The ablation of DAXX results in activation of evolutionarily young LINE1 and ERVs subfamilies. Further study found that reduced H3K9me3 modification and DNA methylation of young LINE1, especially L1Md_A, L1Md_Tf and L1Md_Gf.In summary, this study identifies DAXX as a previously unknown regulator of spermatogenesis and demonstrates that it functions as an epigenetic regulator to maintain the silencing of the young LINE1 Overall design: This study uses whole-genome bisulfite sequencing (WGBS) to characterize DNA methylation dynamics in the testes of P8 wild-type and knockdown mice, with a specific emphasis on methylation changes across genomic regions and transposable element families.