Transcriptional repression during spermatogenesis in C. elegans requires TOP-2, condensin II, and the MET-2 H3K9 methyltransferase.

In C. elegans RNA polymerase II (RNAPII) transcription is globally repressed as oocytes prepare for meiosis. Recent work has identified the transcriptional repressors responsible for genome silencing in oocytes, and they are topoisomerase II ( TOP-2 ), condensin II, the H3K9 methyltransferase SET-25 and MET-2 , and the PIE-1 protein. Here, we focus on TOP-2 , condensin II, and MET-2 and ask if they play a similar role during spermatogenesis. We report that spermatocytes undergo transcriptional repression, as inferred by a deactivation of RNAPII, and this requires TOP-2 , the CAPG-2 subunit of condensin II, and the histone methyltransferase MET-2 .

Characterization of factors that underlie transcriptional silencing in C. elegans oocytes.

While it has been appreciated for decades that prophase-arrested oocytes are transcriptionally silenced on a global level, the molecular pathways that promote silencing have remained elusive. Previous work in C. elegans has shown that both topoisomerase II (TOP-2) and condensin II collaborate with the H3K9me heterochromatin pathway to silence gene expression in the germline during L1 starvation, and that the PIE-1 protein silences the genome in the P-lineage of early embryos. Here, we show that all three of these silencing systems, TOP-2/condensin II, H3K9me, and PIE-1, are required for transcriptional repression in oocytes. We find that H3K9me3 marks increase dramatically on chromatin during silencing, and that silencing is under cell cycle control. We also find that PIE-1 localizes to the nucleolus just prior to silencing, and that nucleolar dissolution during silencing is dependent on TOP-2/condensin II. Our data identify both the molecular components and the trigger for genome silencing in oocytes and establish a link between PIE-1 nucleolar residency and its ability to repress transcription.

A global chromatin compaction pathway that represses germline gene expression during starvation.

While much is known about how transcription is controlled at individual genes, comparatively little is known about how cells regulate gene expression on a genome-wide level. Here, we identify a molecular pathway in the C. elegans germline that controls transcription globally in response to nutritional stress. We report that when embryos hatch into L1 larvae, they sense the nutritional status of their environment, and if food is unavailable, they repress gene expression via a global chromatin compaction (GCC) pathway. GCC is triggered by the energy-sensing kinase AMPK and is mediated by a novel mechanism that involves the topoisomerase II/condensin II axis acting upstream of heterochromatin assembly. When the GCC pathway is inactivated, then transcription persists during starvation. These results define a new mode of whole-genome control of transcription.