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Amith Zafal Abdulla (Brandeis University, USA)

A synthetic epigenetic circuit produces noise-driven heritable oscillations
When Jul 06, 2026
from 10:00 to 11:00
Contact Name Salle des Thèses, Equipe Jost
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In eukaryotes, heritable information is not only genetically encoded but is also stored in the form of covalent histone modifications that can activate or repress transcription. We do not understand how different sources of noise impact the transmission of epigenetic information. Here, we engineer a synthetic negative feedback circuit in fission yeast in which a repressive histone-modifying enzyme suppresses its own expression. Mathematical modeling predicts a stable fixed point with spiraling dynamics, yet in the regime of histone-modification fluctuations, we observe the emergence of sustained noise-driven oscillations. Experimentally, approximately 20% of cell lineages exhibit heritable oscillations persisting over 40 generations, while the remainder stochastically switch between high and low expression states. We show that positive feedback associated with repressive modifications is dispensable for the oscillations. Remarkably, oscillatory dynamics propagate to distal genes, producing correlated oscillations across genomic loci. Our results reveal that epigenetic silencing at this scale (~few nucleosomes) is fundamentally noisy.
 

Contact : D. Jost