Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20−/− spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB) repair. Further investigations reveal that the depletion of RNF20 in the germ cells affects chromatin relaxation, thus preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. The gametogenetic defects of the H2B ubiquitination deficient cells could be partially rescued by forced chromatin relaxation. Taken together, our results demonstrate that RNF20/Bre1p-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation, and suggest an old drug may provide a new way to treat some oligo- or azoospermia patients with chromatin relaxation disorders.

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The functional role of the ubiquitin-proteasome pathway during maternal-to-zygotic transition (MZT) remains to be elucidated. Here we show that the E3 ubiquitin ligase, Rnf114, is highly expressed in mouse oocytes and that knockdown of Rnf114 inhibits development beyond the two-cell stage. To study the underlying mechanism, we identify its candidate substrates using a 9,000-protein microarray and validate them using an in vitro ubiquitination system. We show that five substrates could be degraded by RNF114-mediated ubiquitination, including TAB1. Furthermore, the degradation of TAB1 in mouse early embryos is required for MZT, most likely because it activates the NF-jB pathway. Taken together, our study uncovers that RNF114-mediated ubiquitination and degradation of TAB1 activate the NF-jB pathway during MZT, and thus directly link maternal clearance to early embryo development.

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