The cellular identity of germ cells, the only heritable lineage to the next generation, is distinct from those of somatic lineages. The somatic program is largely suppressed in male germ cells which retain unique cellular identity, passed on to the compacted sperm, and give rise to a totipotent zygote after fertilization. We recently demonstrated that a few thousand genes commonly expressed in somatic lineages and spermatogenesis-progenitor cells (termed somatic/progenitor genes) undergo repression in a genome-wide manner during late stages of the male germline, and identify underlying mechanisms. SCML2, a germline-specific subunit of a Polycomb repressive complex 1 (PRC1), establishes the unique epigenome of the male germline. In the stem cell phase of spermatogonia, SCML2 works with PRC1 and promotes RNF2-dependent ubiquitination of H2A, thereby marking somatic/progenitor genes on autosomes for repression. This repression of somatic/progenitor genes during meiosis and postmeiosis is associated with formation of a novel class of bivalent domains. We infer that the novel bivalent domains allow for the recovery of the somatic/progenitor program after fertilization. Our results uncovered that bivalent H3K27me3 and H3K4me2/3 domains are not limited to developmental promoters (which maintain bivalent domains that are silent throughout the reproductive cycle), but also underlie reversible silencing of somatic/progenitor genes during the mitosis-to-meiosis transition in late spermatogenesis.
Importantly, during spermatogenesis, mechanisms of epigenetic regulation on sex chromosomes differ from autosomes because of meiotic sex chromosome inactivation that is regulated by DNA damage response pathways. X-linked somatic/progenitor genes are suppressed by meiotic sex chromosome inactivation without deposition of H3K27me3. Furthermore, SCML2 also independently prevents RNF2-dependent ubiquitination of H2A on sex chromosomes during meiosis, thereby enabling unique epigenetic programming of sex chromosomes for male reproduction. Taken together, our genome-wide studies reveal epigenetic principles during the mitosis-to-meiosis transition in spermatogenesis.
11 Jul 2016 - 11 Jul 2016