Biology subjects

Chien, E.

Publications and source records attributed to Chien, E..

6 recordsLinked to original sources

bioRxiv2025

A role for the nuclear RNAi pathway in global transcriptional silencing in C. elegans primordial germ cells

In C. elegans, if embryos hatch into an environment lacking nutrients the primordial germ cells (PGCs) will arrest mRNA transcription and enter quiescence until food becomes available. Our previous work had shown that the global transcriptional silencing (GTS) that occurs in PGCs during L1 starvation requires a "hyperdeposition" of the repressive histone mark H3K9me3 in germline chromatin. Hyperdeposition is defined as an increase in the amount of H3K9me3 embedded in germline chromatin, relative to neighboring somatic nuclei. Hyperdeposition initiates in embryonic PGCs and is maintained in starved L1s. Here, we show that the nuclear RNAi pathway contributes to both the initiation and maintenance of H3K9me3 hyperdeposition. Interestingly, both known nuclear Argonautes, HRDE-1 and NRDE-3, play a role in hyperdeposition and they do so in a sequential manner. We show that HRDE-1 acts in embryonic PGCs to initiate hyperdeposition and then, at the embryo-to-L1 transition, HRDE-1 becomes dispensable and NRDE-3 is required to maintain H3K9me3 levels, and for GTS. We also examine the timing of H3K9me3 hyperdeposition and find that it initiates soon after germline zygotic genome activation (ZGA) occurs. Our data suggest a model where ZGA promotes both gene expression and H3K9me3 deposition at active loci, and under starvation conditions these H3K9me3 marks are then employed to silence the germline genome.

developmental biology↗

bioRxiv2025

Testing for a wildlife reservoir of divergent SARS-CoV-2 in white-tailed deer

The 2021 discovery of a divergent lineage (B.1.641) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in white-tailed deer (Odocoileus virginianus) from Ontario raised concerns that deer were a potential reservoir. To assess whether white-tailed deer continued to be infected with B.1.641 and to test for spillover into other species, we established a surveillance program in Ontario by sampling wildlife via existing monitoring programs and through active surveillance of captive and wild animals. Between 2022 to 2024, we tested 2,839 animals, identifying one active SARS-CoV-2 infection (a likely spillover of a recombinant XBB.2.3.11.3 lineage), but no cases of B.1.641. Overall, 93 animals (6.8%) tested positive for SARS-CoV-2 antibodies, including 89 white-tailed deer, two Virginia opossums (Didelphis virginiana), one American mink (Neogale vison), and one river otter (Lontra canadensis). In Southwestern Ontario, where B.1.641 was originally detected, 15.2% of deer samples were seropositive. Generalized Linear Models demonstrated that seropositive deer were more likely to be found in areas with a higher fall deer harvest and human population density, and closer to previous B.1.641 cases. Our data suggest that deer-associated B.1.641 may have caused a relatively localized epizootic without forming a stable reservoir. This study underscores the importance of One Health-focused surveillance.

pathology↗

bioRxiv2022

Astrocyte-like CEPsh glia responds to the stressful environments

While astrocytes are known to be important for development and nourishment of the nervous system, the field is just beginning to explore how astrocytes respond to environmental stimuli. Using Caenorhabditis elegans and their astrocyte-equivalent, CEPsh, we asked whether astrocyte-like glia respond to odor exposure. We found one day-old adult C. elegans decrease hlh-17 promoter (CEPsh glia marker) mediated fluorescent expression when trained with an innately attractive odor butanone. Moreover, the olfactory training paradigm itself affects phlh-17 expression, but in a different way. This suggests astrocyte-like CEPsh glia can integrate environmental information to respond to changes in the environment, which enhances survival.

animal behavior and cognition↗

bioRxiv2022

The TOP-2-condensin II axis silences transcription during germline specification in C. elegans

In C. elegans, the germline is specified via a preformation mechanism that relies on the PIE-1 proteins ability to globally silence mRNA transcription in germline precursor cells, also known as the P-lineage. Recent work from our group has identified additional genome silencing events in C. elegans during oogenesis and in starved L1 larvae, and these require the condensin II complex, topoisomerase II (TOP-2), and components of the H3K9me/heterochromatin pathway. Interestingly, silencing in oocytes also requires PIE-1, but this is not the case in starved L1s. Here, we ask if additional genome silencing components besides PIE-1 are required to repress gene expression in the P-lineage of early embryos, and we find that condensin II and TOP-2 are required and the H3K9me/heterochromatin pathway is not. We show that depletion of condensin II/TOP-2 activates the normally suppressed RNA polymerase II to inappropriately transcribe somatic genes in the P-lineage. We also present evidence that while both PIE-1 and condensin II/TOP-2 are required for genome silencing in the P-lineage, PIE-1 can silence transcription independently of condensin II/TOP-2 when misexpressed in somatic cells. Thus, in oocytes, all three genome silencing systems (TOP-2/condensin II, H3K9me, and PIE-1) are operational while in both early embryos and starved L1s two of the three are active (TOP- 2/condensin II and PIE-1 for early embryos, TOP-2/condensin II and H3K9me for starved L1s). Our data show that multiple, redundantly acting genome silencing mechanisms act in a mix and match manner to repress transcription at different developmental stages in the C. elegans germline.

developmental biology↗

bioRxiv2022

The global chromatin compaction pathway silences transcription during meiotic prophase in C. elegans

Abstract/SummaryWhile 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.

developmental biology↗

bioRxiv2022

Highly divergent white-tailed deer SARS-CoV-2 with potential deer-to-human transmission

Wildlife reservoirs of SARS-CoV-2 may enable viral adaptation and spillback from animals to humans. In North America, there is evidence of unsustained spillover of SARS-CoV-2 from humans to white-tailed deer (Odocoileus virginianus), but no evidence of transmission from deer to humans. Through a biosurveillance program in Ontario, Canada we identified a new and highly divergent lineage of SARS-CoV-2 in white-tailed deer. This lineage is the most divergent SARS-CoV-2 lineage identified to date, with 76 consensus mutations (including 37 previously associated with non-human animal hosts) and signatures of considerable evolution and transmission within wildlife. Phylogenetic analysis also revealed an epidemiologically linked human case. Together, our findings represent the first clear evidence of sustained evolution of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission.

microbiology↗