This work was spearheaded by Koen Flach and Moreno Martinovic. It was performed at the @nkinl.bsky.social and funded by @erc.europa.eu and NWO.
Posts by Elzo de Wit lab @ NKI
Conclusion: the Sox2–SCR loop is a multicomponent system. Loop extrusion, chromatin dynamics, enhancer activity, and backup elements each contribute. Equivalent disruptions of contact frequency can yield divergent transcriptional outcomes. Details matter. doi.org/10.1101/gad.353296.125
Allele-specific epigenetic silencing of the SCR confirmed this in cis: loop frequency dropped on the inactive allele but was partially maintained. Combining SCR inactivation with RAD21 depletion reduced contacts to near-background — indicating they are additive.
BET inhibition (iBET151/JQ1) mildly reduced Sox2–SCR contacts. Combined with RAD21 depletion, the effects were additive — not epistatic. Cohesin-mediated loop extrusion and enhancer-bound BET proteins maintain the loop through independent mechanisms.
(Our inspiration for the SRR2 came from @elphegenoralab.bsky.social beautiful recent paper: www.science.org/doi/10.1126/.... Check it out for more details on SRR2)
We deleted SRR2 — a weak enhancer 3 kb downstream of Sox2 with no solo effect on expression. In CTCF-depleted cells, SRR2 deletion dropped Sox2 to ~54%. A functionally silent element becomes an essential buffer under stress.
Our model: WAPL depletion rigidifies chromatin by locking cohesin at CTCF sites. This restricts locus mobility, reducing productive Sox2–SCR encounters even when contact frequency (by 4C) appears similarly reduced to RAD21 depletion.
Paradoxically, stabilising cohesin by depleting WAPL — despite keeping more cohesin on chromatin — caused a rapid ~30–52% drop in Sox2 expression. Same reduction in Sox2–SCR contacts, very different transcriptional outcome.
Using AID degron lines, acute depletion of cohesin (RAD21) or CTCF caused only mild Sox2 downregulation (~27%). Sox2–SCR contact frequency dropped, but expression was largely maintained.
New paper in Genes & Dev: we dissected how Sox2 — a key pluripotency TF — is regulated by a distal enhancer cluster (SCR) 100 kb away. The results challenge simple models of cohesin-mediated loop extrusion of gene regulation. genesdev.cshlp.org/content/earl... 🧵
Harvey Yang and I were fortunate to contribute polymer simulations to this paper from @nicholas-aboreden.bsky.social Zhao... Zhang, Blobel showing that most CRE loops can form de novo after mitosis without loop extrusion
www.nature.com/articles/s41...
Germ cells have their own versions of core transcription factors and fertility depends on them.
We're hiring a PhD student to figure out how! 📢
Fly genetics + proteomics + genomics. Fully funded.
Aarhus University 🇩🇰
Deadline May 1 👇
Please share with anyone who might be interested!
Model of the C. elegans condensin I(DC) complex
Our new preprint in collaboration with @meisterpeterf.bsky.social uncovers the molecular basis for condensin recruitment to X chromosomes in C. elegans and reveals atomic-level details of a previously unknown auto-inhibited state of condensin.
www.biorxiv.org/cgi/content/short/2026.03.13.711519v1
The newly established NeCEN Utrecht is looking for a #cryoEM scientist!
www.uu.nl/en/organisat...
Work with a new Krios 5 + pFIB and support cutting-edge life science research.
📍 Utrecht | 🗓 Apply by 30 April
Please share with your network!
We’re recruiting new Research Group Leaders. We offer:
🔬 World-class IT infrastructure
🧠 Creative freedom for your research
📊 Access to the world’s most comprehensive open biological data
Apply by 11 April embl.wd103.myworkdayjobs.com/en-US/EMBL/j...
#ResearchCareers @johnlees.bacpop.org @embl.org
Thanks @the-node.bsky.social @biologists.bsky.social for allowing spreading the word
@kawresearch.bsky.social @scilifelab.se @remeseiro-lab.bsky.social
thenode.biologists.com/join-the-sum...
Our paper is now out in Nature:
“Ancient co-option of LTR retrotransposons as yeast centromeres”
www.nature.com/articles/s41...
A short thread on how retrotransposons helped give rise to yeast point centromeres.
1/14
🔥 How does CTCF shape enhancer–promoter communication?
In our new preprint, we systematically test how the position and orientation of CTCF binding sites (CBSs) influence gene regulation at the mouse Sox2 locus.
🧪 full paper can be found here: www.biorxiv.org/content/10.6...
We are looking for a new group leader to join the IGH (Montpellier, France). I can’t wait to meet my future colleague! Apply :-) More infos here: igh.cnrs.fr/join-igh-as-...
That sounds like a great idea😁
Previously on @biorxiv-plants.bsky.social now in final published version: www.nature.com/articles/s41...
Thanks, Edda!
Thanks! Happy to discuss😁
Thanks, Dario! How’s life?
New preprint from our lab... We applied our hopping technology to relocate CTCF binding sites to thousands of alternative positions in the Sox2 locus: www.biorxiv.org/content/10.6...
Thanks, Fra!
Thanks!
Thanks!
The zebrafish knock-outs still have maternally deposited CTCF, so this may also pull them through gastrulation. But is interesting to think how this could be conserved between species.