Thanks Agnese!! 😄

Glad you like it! Really appreciated having your feedback along the way!

Thanks! That sounds like an exciting application indeed, long reads could definitely open up new possibilities for repetitive regions!
Best of luck if you give it a try, and feel free to reach out if you want to discuss ideas further! 😊

Thank you Gemma!!

ChromSMF opens the door to study:
✅ how multi-layer gene regulation is coordinated
✅ how TF binding and chromatin state influence each other
✅ how chromatin states change over time

All in one assay ⚙️🧩.

Check it out, we are curious to know what you think! 🙌 www.biorxiv.org/content/10.6...

8/8

Because sequence information is preserved, we also get allele-specific chromatin states, even without a reference genome! 🧬

Haplotype-aware epigenomics analysis unlocked! 🔓

7/8

Long reads add another dimension 🔗

Ever wondered about long-range relationships between histone modification and chromatin accessibility? ChromSMF can now link chromatin features across multi-kb regions on the same molecule!!

Look how this entire locus is kept open when H3K27ac is present! 🔥

6/8

We applied ChromSMF to profile:

🟢 three active marks (H3K4me3, H3K27ac, H3K4me1)
🛑 two repressive marks (H3K27me3, H3K9me3)

in Drosophila 🪰 and mouse 🐭 cell lines.

5/8

Why does it matter? 🤔

At any locus, we can now directly:
• measure epigenetic heterogeneity
• quantify combinatorial chromatin states
• link regulatory layers without averaging

These mixed states are largely invisible in bulk assays 👀

4/8

The idea?
Combining multiple signals into one readout!

👣 cytosine methylation footprinting → protein-DNA interactions
🎯 antibody-guided adenine methylation → histone modifications
🧬 Nanopore sequencing → direct methylation detection on long reads

→ one molecule, multiple regulatory layers 🔗🧩

3/8

In a single ChromSMF experiment, we can profile:
1️⃣ Chromatin Accessibility
2️⃣ Histone Modifications
3️⃣ TF binding
4️⃣ DNA methylation

All together, genome-wide, on single multi-kb long DNA molecules 🧬

2/8

ChromSMF preprint is out!🚀
tinyurl.com/ChromSMF

We often piece together chromatin regulation layer by layer from separate assays. But this can be limiting!

In @arnaudkr.bsky.social's lab, we developed a method to directly study multiple layers on the same DNA molecule! 🧬

What does this unlock? ⬇️

Tomorrow I’ll be presenting at the 2026 CSHL Systems Biology meeting! 🧬

Join to hear about ChromSMF, a genomic method for integrated measurement of histone modifications, protein-DNA interactions, and DNA methylation on the same multi-kilobase DNA molecules! 🚀

Preprint coming soon 😉

First time posting here — and first-ever Single Molecule Conference 🧬

Held right at @embl.org Heidelberg, where I work!

4 days full of great science and great people. Fantastic meeting! 🔬

Curious to see where the single molecule field is going next! 👀

#EMBLSingleMolecule @events.embl.org