The germline is the only heritable lineage across generations. It remains unknown how the germline epigenome is distinctly established from that of somatic lineages. We recently demonstrated that 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 through two distinct antithetical mechanisms on autosomes and sex chromosomes, respectively. 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 that allow for the recovery of the somatic/progenitor program after fertilization.
Our results suggest 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. On the other hand, induction of late spermatogenesis genes is facilitated by poised chromatin established in the stem cell phases of spermatogonia. Taken together, our genome-wide studies revealed epigenetic principles during the mitosis-to-meiosis transition in spermatogenesis. My study will reveal fundamental epigenetic mechanisms in the male germline and help illuminating various reproductive issues including male infertility and birth defects.
Figure 3 - Global transcriptome changes during the late stages of the male germline and a model. (A) A heat map showing gene expression patterns among several germ cell types versus somatic cells. ES: embryonic stem cells, GS: germline stem cells, THY+: THY1+ undifferentiated spermatogonia, PS: pachytene spermatocytes, RS: round spermatids, and MEF: mouse embryonic fibroblasts. All 16,475 genes that showed more than 3 RPKM (Reads per kilo base per million mapped reads) in at least one cell type are shown. (B) Model of the gamete-to-embryo transition. Hasegawa et al., Dev Cell 2015, Sin et al., BMC Biol 2015.