During spermatogenesis, extensive chromatin remodeling and histone replacement reshape the male germline epigenome. Although HIRA mediates transcription-coupled incorporation of histone variant H3.3, we identified DAXX as a key histone chaperone directing genome-wide, transcription-coupled replacement of H3.4 (H3T) with H3.3 on autosomes during male meiosis. Simultaneously, DAXX also directs transcription-independent H3.4-to-H3.3 replacement on the sex chromosomes during meiotic sex chromosome inactivation (MSCI). These distinct, chromosome-specific modes of DAXX-mediated H3.3 deposition are essential for epigenomic integrity in the male germline. Loss of DAXX disrupts this process, resulting in widespread transcriptional dysregulation in haploid round spermatids and impaired male fertility.
Yeh et al. (Tue,) studied this question.