The scaffold protein SIN3 aids the assembly of distinct complexes containing histone deacetylases (HDACs). These complexes modulate gene expression via chromatin modifications, but their specific functions during development are unclear. Here, Francesca Palladino, Cecile Bedet, Valérie Robert and colleagues use CRISPR/Cas9 to produce a full knockout of sin-3, the Caenorhabditis elegans SIN3 homologue. They show that lack of SIN-3 expression results in maternal effect sterility and reduced proliferation of germ cell progenitors. These effects do not seem to be due to specific disruption of genes involved in oogenesis. Instead, the authors find that a significant proportion of upregulated genes in the sin-3 mutant worms are on the X chromosome, and single-molecule fluorescence in situ hybridisation shows that these mutants exhibit premature X transcript expression during oogenesis. This suggests that SIN-3 plays a role in X chromosome silencing. Immunoprecipitation and mass spectrometry experiments reveal the presence of at least two distinct SIN-3 complexes in worms that contain different HDACs. Depletion of different subunits from the two complexes has varying effects on the germline, suggesting that these complexes contribute to fertility in different ways. Overall, this work identifies a crucial role for SIN-3 in oogenesis and begins to untangle the regulatory functions of distinct SIN-3 complexes.
