Spermatogenesis is supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs). These cells can transmit genetic and epigenetic information, but how they contribute to inter-generational epigenetic inheritance is unclear. Now, Kazuyuki Ohbo and colleagues report that Kmt2b, which is a H3K4 methyltransferase, primes SSCs to regulate gene expression both within the germline and in the next generation. They first show that Kmt2b is highly expressed in SSCs, and that its loss impairs the SSC-to-progenitor transition. Using ChIP-seq, the authors demonstrate that Kmt2b targets ‘bivalent’ promoters that carry both active (H3K4me3) and silent (H3K27me3) marks, and that are implicated in cell differentiation and commitment. However, the authors also note that Kmt2b targets promotors that lack H3K27me3; these targets, which the authors term ‘monovalent genes’, are instead implicated in biosynthetic and signalling pathways. Further analysis of these two gene sets reveals that Kmt2b-dependent monovalent genes are upregulated during late spermatogenesis, whereas most bivalent genes are not activated until post-fertilization development. Overall, these findings lead the authors to propose that Kmt2b acts as a priming factor in SSCs that marks two distinct sets of promoters – one activated in the germline and the other in the next generation.
