Daniel Jost - Physical Biology of Chromatin group
@djost-physbiol.bsky.social
220 followers 220 following 14 posts
CNRS Senior Researcher - Group Leader at Laboratory of Biology and Modeling of the Cell, Ecole Normale Supérieure de Lyon. Physical biology of chromatin: modeling the spatio-temporal dynamics of eukaryotic genomes.
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djost-physbiol.bsky.social
Chromatin gets stiffer when pulled gently but softer when yanked hard—thanks to loop extrusion. SMCs may play the role fo shock absorbers, protecting the genome from weak mechanical perturbations but allowing adaptation for persistent strong stresses.
djost-physbiol.bsky.social
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💡 Big picture:
Replication doesn’t just use the genome’s 3D structure—it actively reshapes it.
Our model bridges replication dynamics with genome architecture, offering a new view of chromatin duplication in 3D.
djost-physbiol.bsky.social
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Our model also reveals a dynamic effect:
As forks move, they temporarily slow down chromatin motion.
Why? Due to the mechanical constraints of fork passage and intertwining of sister chromatids. 🧷
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Zooming out: replication forks are not evenly spread in early S-phase.
They concentrate at one nuclear pole, then redistribute more evenly later on.
This spatial bias could explain how forks cluster into Replication Foci, seen in microscopy! 🧪
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Then we asked: does this pattern exist in real cells?
✅ We confirmed it in vivo using new Hi-C data collected during early S-phase thanks to a collaboration with @aurelepiazza.bsky.social
And it holds across different conditions.
Importantly, it’s:
🔄 Replication-dependent
🚫 Cohesin-independent
djost-physbiol.bsky.social
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What did we find?
A striking “fountain” pattern forms around early origins of replication, caused by the colocalization of sister forks moving outward.
This pattern emerges spontaneously from our model! 🚰
djost-physbiol.bsky.social
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We built a computational model of the yeast genome that integrates:
📍Realistic 3D chromatin architecture
🕒 Accurate replication timing
With this, we simulated how replication unfolds spatially inside the nucleus.
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DNA replication doesn’t happen in isolation—it’s tightly linked to how chromatin is organized in space.
But from the behavior of sister replication forks to the formation of replication domains, many mechanisms are still debated. So, we turned to modeling. 💻
djost-physbiol.bsky.social
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How does DNA replication shape the 3D structure of the genome? 🧬
Despite major advances, we still don’t fully understand how replication and chromosome architecture interact. In our new study, we dive into this interplay using Saccharomyces cerevisiae as a model. 🔬
djost-physbiol.bsky.social
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