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.
While it has been appreciated for decades that prophase-arrested oocytes are transcriptionally silenced, the molecular pathway that promotes silencing has remained elusive. Here, using C. elegans as a model system, we demonstrate that the global chromatin compaction (GCC) pathway is responsible for genome silencing in both oocytes and spermatocytes. GCC is mediated by a collaboration between topoisomerase II, condensin II, and the H3K9me pathway. For oocytes, we further demonstrate that GCC is under cell cycle control such that it is activated specifically during diakinesis and prior to oocyte maturation. Previous work had shown that GCC silences gene expression in the primordial germ cells (PGCs) of nutrient-deprived L1 larvae, and we demonstrate here that it is also used during gametogenesis, thus showing that GCC is a versatile, signal-mediated genome silencing system.
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.
We performed a laboratory experiment on caged, domesticated Australian Zebra Finches (Taeniopygia guttata castanotis) to assess the effects of antimicrobial treatment applied to birds’ plumage on the feather microbial loads of breeding pairs and their associated reproductive performance. Treatments included an experimental group that experienced frequent misting with a broad-spectrum antimicrobial, as well as 2 control groups. Microbial loads (colony forming units [CFUs]) sampled from the belly feathers of breeders were higher post-hatching than pre-hatching, and experimental pairs had lower loads (one-half to one-third the CFU counts) than controls at all sampled breeding-cycle stages. Clutch size and hatching success did not differ among treatments, but experimental pairs fledged nearly 50% more offspring (mean = 3.5 per clutch) than controls (mean = 2.3 per clutch) due to experiencing much lower nestling mortality. Offspring development rate, as assessed by one metric, varied among treatments: beak color score sampled midway in the development of adult phenotype revealed that offspring of experimental pairs had more rapid development. Findings imply that experimentally reduced density of feather microbial loads on breeders decreased reproductive costs in the post-hatch phase, resulting in increased offspring survival and condition. At the time offspring fledged, uropygial gland volume tended to be greater among breeders that had experienced antimicrobial application throughout the breeding cycle. These results are consistent with a growing literature showing that the feather microbiome contributes significantly to the evolution of avian life histories and behavior and indicate that Zebra Finches are a useful laboratory model for investigating in vivo effects of the feather microbiome on avian hosts.
In many organisms, mRNA transcription must be globally repressed in germline precursor cells during specification for them to maintain a germline fate. In C. elegans, germline precursor cells are known as the P lineage, and it is the PIE-1 protein that is responsible for silencing transcription in these cells. Loss of PIE-1 results in a fate switch, whereby the P2 cell loses germline fate and instead adopts a somatic fate. Previous work had also defined a global chromatin compaction (GCC) pathway that silences transcription in oocyte, spermatocytes, and primordial germ cells in C. elegans. GCC silencing requires the topoisomerase II (TOP-2)/condensin II chromatin compaction pathway together with components of H3K9me pathway. These factors come together to promote a global compaction of chromatin, thereby silencing gene expression. The goal of this study was to ask if the GCC pathway is also important for genome silencing in the P lineage. We report that GCC per se is not required, as we find that the H3K9me pathway is dispensable for transcriptional repression in P cells. However, we do uncover a critical role for TOP-2/condensin II in P-cell silencing. Loss of TOP-2 and/or the CAPG-2 subunit of condensin II leads to active, elongating RNA polymerase II in P cells, leading to expression of both somatic and germline genes. These data shed new light on how transcription is regulated during germline specification.
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