🚨 new preprint from the lab. Combining modeling, new Hi-C data in yeast and data analysis, our study offers new insights into the spatial and dynamic organization of chromatin during replication in eukaryotes. Check the tweetorial below ⬇️ https://www.biorxiv.org/content/10.1101/2025.04.23.650322v1
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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. 🔬
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. đź’»
We built a computational model of the yeast genome that integrates:
đź“ŤRealistic 3D chromatin architecture
đź•’ Accurate replication timing
With this, we simulated how replication unfolds spatially inside the nucleus.
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! đźš°
Then we asked: does this pattern exist in real cells?
âś… 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
đźš« Cohesin-independent
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! 🧪