Kmt2b conveys monovalent and bivalent H3K4me3 in spermatogonial stem cells at germline and embryonic promoters. Mus musculus

The mammalian male germline is sustained by a pool of spermatogonial stem cells (SSCs) that can transmit both genetic and epigenetic information to offspring. However, the mechanisms underlying epigenetic transmission remain unclear. The histone methyltransferase Kmt2b is highly expressed in SSCs and required for the SSC-to-progenitor transition. At the stem cell stage, Kmt2b catalyzes H3K4me3 at bivalent H3K27me3-marked promoters as well as at promoters of a new class of genes lacking H3K27me3, which we call monovalent. Monovalent genes are mainly activated in late spermatogenesis while the bivalent genes are mainly not expressed until embryonic development. These data suggest that SSCs are epigenetically primed by Kmt2b in two distinguishable ways for the upregulation of gene expression during the spermatogenic program and through the male germline into the embryo. Because Kmt2b is also the major H3K4 methyltransferase for bivalent promoters in embryonic stem cells, we also propose that Kmt2b has the capacity to epigenetically prime stem cells. Overall design: ChIP-seq (H3K4me3 and H3K27me3) and RNA-seq were performed using Kmt2b control (F/F) and knockout (FC/FC) germline stem cells (GSCs). H3K9me3 ChIP-seq was performed using Kmt2bF/F samples. All experiments were done using duplicate cell lines.