Biology subjects

Methot, S.

Publications and source records attributed to Methot, S..

3 recordsLinked to original sources

bioRxiv2025

A scheduler for rhythmic gene expression

Genetic oscillators drive precisely timed gene expression, crucial for development and physiology. Using the C. elegans molting clock as a model, we investigate how oscillators can schedule the orderly expression of thousands of genes. Single cell RNA sequencing reveals a broad peak phase dispersion in individual issues, mirrored by rhythmic changes in chromatin accessibility at thousands of regulatory elements identified by time-resolved ATAC-seq. We develop a linear model to predict chromatin dynamics based on the binding of >200 transcription factors. This identifies nine key regulators acting additively to determine the peak phase and amplitude of each regulatory element. Strikingly, these factors can also generate constitutive, non-rhythmic activity through destructive interference. Validating its power, the model accurately predicts the impact of GRH-1/Grainyhead perturbation on both chromatin and transcript dynamics. This work provides a conceptual framework for understanding how combinatorial, non-cooperative transcription factor binding schedules complex gene expression patterns in development and other dynamic biological processes.

systems biology↗

bioRxiv2025

ATRX safeguards cellular identity during C. elegans development

ATRX is a member of the SWI/SNF family of ATP-dependent chromatin remodellers. In humans, loss of ATRX function leads to ATRX syndrome, a neurodevelopmental disorder. ATRX mutation in human cell lines is associated with multiple phenotypes including activation of the alternative lengthening of telomere (ALT) pathway, upregulation of retrotransposons and increased sensitivity to replication stress. However, the principal role of ATRX and the reason why its mutation causes such diverse phenotypes is currently unclear. To address this, we studied the role of ATRX in the model organism Caenorhabditis elegans. We find that loss of XNP-1, the C. elegans homologue of ATRX, recapitulates many human phenotypes. Loss of XNP-1 causes ectopic activation of germline genes in somatic cells, indicating a loss of cellular identity control. Strikingly, mutation of the germline transcription factor gsox-1 suppresses both this misexpression and multiple xnp-1 phenotypes, including developmental delay and telomeric defects. These findings suggest that ectopic germline gene expression underlies the majority of XNP-1-dependent phenotypes, consistent with a role for XNP-1 in maintaining cellular identity, offering insights into the functions of ATRX in humans.

molecular biology↗

bioRxiv2022

Impact of growth-promoting alternatives on weight gain and gut microbial diversity and activity in piglets

In swine husbandry, weaning is a critical event for piglets which causes environmental, nutritional, and psychological stresses, with consequences such as intestinal dysbiosis. To counteract this issue, producers resorted to the use of in-feed antimicrobials to prevent post-weaning diarrhea and to promote growth for increased animal performance. However, the use of antibiotic for growth promotion was banned in many countries. In-feed supplements have great potential as alternative strategies. This study evaluated the effect on gut microbial activity, microbiome, and animal performance of combinations of peri-weaning feeding strategies such as bovine colostrum, medium-chain fatty acids and yeast extract. We quantified weight gain, intestinal pH, volatile fatty acids, and characterized the gut microbiota on ileum, cecum, and colon digestates. Overall, the feed supplements had limited impact on weight gain and volatile fatty acids production. However, the combined treatments have demonstrated a modulatory effect on gut microbiota which supports a potential role as an alternative to growth-promoting antibiotic in the swine industry.

microbiology↗