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Broad H3K4me3 controls transcription output and timing during spermatid development

ABSTRACT: Male germ cells express a complex transcriptome under tight temporal regulation during their development. However, our knowledge of the epigenetic regulation of crucial stages in this process, such as meiotic onset, remains limited. Here, by dissecting a comprehensive map of the dynamic epigenomic landscape in developing mouse male germ cells, we uncover mutually exclusive shifts in the repressive histone marks H3K9me2, H3K9me3 and H3K27me3 during the mitosis-to-meiosis transition and completion of meiotic recombination. These dynamic shifts coincide with temporal changes in global transcriptional output, retrotransposon activity, and the silencing of mitotic/meiotic genes during spermatogenesis. In addition, we identify Setd1b-mediated broad H3K4me3 domains in both mouse and human spermatids. These broad H3K4me3 domains promote Pol II occupancy and transcription, resulting in high gene expression in spermatids. Setd1b ablation leads to a complete loss of broad H3K4me3, and the redistribution of Pol II from broad H3K4me3 promoters to regular H3K4me3 promoters, thereby compromising temporal gene expression and ultimately hampering spermiogenesis. These findings reveal that dynamic epigenetic changes orchestrate stage-specific gene expression in spermatogenesis, with Setd1b-mediated broad H3K4me3 serving as a crucial regulator that controls the timing of stage-specific gene expression in spermatids.

ORGANISM(S): Mus musculus

PROVIDER: GSE242515 | GEO | 2024/09/03

REPOSITORIES: GEO

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