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The Groth lab @grothlab.bsky.social · 21/08/2026

6/7 Using machine-learning and our single-molecule data, we found nucleosome depletion and irregular, long nucleosome spacing underly AMC-forming genes. Preventing new histone deposition by CAF-1 also causes AMC formation ➡️ thus, 𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐨𝐦𝐞 𝐨𝐫𝐠𝐚𝐧𝐢𝐳𝐚𝐭𝐢𝐨𝐧 𝐜𝐚𝐧 𝐝𝐲𝐧𝐚𝐦𝐢𝐜𝐚𝐥𝐥𝐲 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐞 𝐠𝐞𝐧𝐨𝐦𝐞 𝐚𝐫𝐜𝐡𝐢𝐭𝐞𝐜𝐭𝐮𝐫𝐞 🧬

How nucleosome occupancy on single chromatin fibres upon FACT-depletion differs in AMC vs. non-AMC regions. Figure adapted from Figure 6, Frater et al. (2025), bioRxiv, 2026.02.25.707725. Reproduced with permission from the copyright holder.

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The Groth lab @grothlab.bsky.social · 21/08/2026

5/7 A big surprise came when we looked at the 3d genome of FACT-depleted cells. Many highly-transcribed genes coalesce into 𝐚𝐛𝐞𝐫𝐫𝐚𝐧𝐭 𝐦𝐢𝐜𝐫𝐨-𝐜𝐨𝐦𝐩𝐚𝐫𝐭𝐦𝐞𝐧𝐭𝐬 (𝐀𝐌𝐂𝐬). These extended gene-gene interactions, not enriched for PolII & cohesion, led to our hypothesis that these interactions are affinity-driven.

Micro-C heat map showing aberrant micro compartments forming in FACT-depleted cells. Figure adapted from Figure 5, Frater et al. (2025), bioRxiv, 2026.02.25.707725. Reproduced with permission from the copyright holder.

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The Groth lab @grothlab.bsky.social · 21/08/2026

4/7 Without FACT histone recycling, histone modifications are massively lost across active genes, even with H3.3 deposition partially restoring nucleosome occupancy. ➡️Recycling of old modified histones through transcription is therefore critical to maintain active chromatin states.

Graph showing the relative levels of various histone marks and H3.3 across highly transcribed genes in FACT-depleted cells. Figure adapted from Figure 4, Frater et al. (2025), bioRxiv, 2026.02.25.707725. Reproduced with permission from the copyright holder.

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The Groth lab @grothlab.bsky.social · 21/08/2026

3/7 With @vram142.bsky.social‘s RASAM, we see the disruption of nucleosomes and their spacing in the wake of replication upon FACT depletion. The same is seen in the wake of transcription, but to a greater degree: chromatin fibre structure collapses ➡️ 𝐅𝐀𝐂𝐓 𝐢𝐬 𝐚 𝐮𝐧𝐢𝐯𝐞𝐫𝐬𝐚𝐥 𝐡𝐢𝐬𝐭𝐨𝐧𝐞 𝐫𝐞𝐜𝐲𝐜𝐥𝐞𝐫. ♻️

Single-molecule chromatin fibre accessibility patterns for different quartiles of expressed genes in FACT-depleted and control cells. Figure adapted from Figure 3, Frater et al. (2025), bioRxiv, 2026.02.25.707725. Reproduced with permission from the copyright holder.

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The Groth lab @grothlab.bsky.social · 14/01/2026

Congratulations to @groth-anja.bsky.social on receiving the Novo Nordisk Foundation Jacobæus Prize 🏆 we’re proud to see Anja's mentorship, leadership, & pioneering work in epigenetic cell memory getting top recognition 👏 celebrating the contributions of past & present lab members to this work too 🥳

A picture of current members of the Groth lab

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The Groth lab @grothlab.bsky.social · 28/08/2025

We have lift off!! 🚀 Yesterday was the official opening of EpiC! The DNRF Center for Epigenetic Cell Memory at the Danish Cancer Institute! Our EpiC team with director Anja Groth @groth-anja.bsky.social, were joined by Jesper Fisker, CEO @cancer.dk & Niels Mejlgaar, CEO @dg.dk to celebrate 🎉

Image of Niels Mejlgaar (CEO of DNRF), Anja Groth (EpiC director) & Jesper Fisker (CEO of DCS).

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The Groth lab @grothlab.bsky.social · 27/06/2025

Congratulations to Ada 🥳🍾, who very successfully defended her master's thesis today! You were an excellent student and we were super happy to have you in the lab! Wishing you all the best for the future and enjoy your well-deserved break!

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The Groth lab @grothlab.bsky.social · 06/03/2025

So, how does CODANIN-1 bind ASF1? Our cryo-EM structure reveals that CODANIN-1 forms a dimer, with each monomer binding two ASF1A molecules. These two ASF1As are held in proximal and distal positions by CODANIN’s N-terminal B domain (BD-N) and C-terminal histone H3 mimic helix (HMH-C), respectively.

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The Groth lab @grothlab.bsky.social · 19/02/2025

Our work highlights 𝐩𝐚𝐫𝐞𝐧𝐭𝐚𝐥 𝐡𝐢𝐬𝐭𝐨𝐧𝐞 𝐫𝐞𝐜𝐲𝐜𝐥𝐢𝐧𝐠 𝐚𝐬 𝐚 𝐤𝐞𝐲 𝐞𝐩𝐢𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐬𝐚𝐟𝐞𝐠𝐮𝐚𝐫𝐝 – histone modifications must be 𝐞𝐟𝐟𝐢𝐜𝐢𝐞𝐧𝐭𝐥𝐲 transmitted to 𝐛𝐨𝐭𝐡 daughter strands for this to work! Could failures in this process contribute to developmental disorders, cancer, or aging? More to explore! 4/n

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The Groth lab @grothlab.bsky.social · 20/12/2024

Exciting news!🌟 Together with Alexander van Oudenaarden, @jervdberg.bsky.social and @lleonie.bsky.social, we’ve been awarded a €2M NNF Synergy grant. We're thrilled to collaborate🤝 and to develop cutting-edge single-cell and single-molecule methods for replication and chromatin research! 🚀

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