2025/09/04 by Dimos Gaidatzis, Maike Graf-Landua, Stephen P. Methot +11 · 2 voices
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Genetics, Aging, and Longevity in Model Organisms #Gene Regulatory Network Analysis #Circadian rhythm and melatonin
paper · pdf · doi:10.1101/2025.09.04.674194
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.