Raphaël Pantier

The gene-regulating proteins NONO and SFPQ assemble into ordered filaments - Communications Biology Filament formation of full-length NONO/SFPQ heterodimers was observed and structurally characterized in vitro which may provide a scaffold for gene regulation, paraspeckle formation and DNA double-str...

Much enjoyed this nice cryoEM study of NONO:SFPQ heterocomplex this morning, while it was snowing outside. So happy to read a paper in full again (only a handful of papers read in full in last weeks or even months ☹, and some were to review).

Postdoc position available in our lab @igbmc.bsky.social
We have an exciting project aimed at re-visiting the (epi-)genomic functions of AT-binding proteins using state-of-the-art technologies: www.igbmc.fr/en/igbmc/lif...
Expected start: from March 2026
Please share 📢

Thanks very much Brian for your positive feedback! :)
It would be interesting to see if this kind of approach can be applied to other chromatin-binding proteins regulating transcription globally.

Single-Molecule DNA Footprinting and Transcription Imaging Reveal the Molecular Mechanisms of Promoter Dynamics https://www.biorxiv.org/content/10.1101/2025.11.26.690466v1

8/8 In conclusion, our work shows that:
1- SALL4 function relies entirely on multimerisation via a conserved Q-rich region mutated in human diseases (Giuliani et al).
2- SALL4 is an atypical transcription factor modulating the epigenome via dispersed binding to AT-rich DNA (Chhatbar et al).

7/8 To gain further mechanistic insight, we designed mutagenesis and domain swap experiments in stem cells and animal models. This showed that recruitment of the chromatin remodelling complex NuRD is essential for SALL4 function in vivo.

6/8 Combining acute degradation with multi-omics and explainable machine learning, we uncovered a crucial role for dispersed SALL4 binding over gene bodies. SALL4 influences chromatin structure at both transcriptionally “active” and “silent” regions, indicating a primary action on the epigenome.

Pervasive binding of the stem cell transcription factor SALL4 shapes the chromatin landscape Mechanistic understanding of how gene activity is regulated has focussed on the roles of transcription factors at promoters and enhancers, whereas mechanisms capable of globally fine-tuning gene expre...

5/8 Second, we explored the action of SALL4 on the (epi-)genome of stem cells 🧬 This transcription factor has a preference for short AT-rich motifs which are very frequent and dispersed across the genome, so how does this protein control gene expression?
doi.org/10.1101/2025...

4/8 Additionally, we modelled patient variants in SALL4 and SALL1 using cellular and animal models, demonstrating that multimerisation is involved in the pathogenesis of both Okihiro (OS) and Townes-Brocks (TBS) syndromes.

3/8 We mapped an evolutionarily conserved Q-rich Interaction Domain (QID) responsible for the formation of tetrameric SALL complexes. Strikingly, mutation of this domain within SALL4 (forcing the protein to become monomeric) abolishes chromatin binding and mimics a complete knockout!

Tetramerisation governs SALL transcription factor function in development and disease Spalt-like (SALL) proteins are C2H2 zinc-finger transcription factors important for embryogenesis, with mutations in SALL1 and SALL4 causing rare congenital disorders Townes-Brocks and Okihiro syndrom...

2/8 First, we investigated the rules of assembly. 🧩 SALL4 is known to homo- and hetero-multimerise with other SALL proteins, but the molecular basis and biological relevance of these protein interactions remained unclear.
doi.org/10.1101/2025...

1/8🧵 Excited to share two studies in which I was involved within the Bird Lab📄📄 We have explored how the transcription factor SALL4 assembles and shapes chromatin in embryonic stem cells.
@kashyapchhatbar.bsky.social @saragiuliani.bsky.social @drphcb-uoe.bsky.social @edinburghbiology.bsky.social

The IGBMC is recruiting a new Computational Biology Group Leader through the ENACT AI Chair for Scientific Discoveries, covering cancer, developmental, and structural biology. Join one of Europe’s leading life science centers!
cluster-ia-enact.ai/appels-a-pro...
Deadline: Jan 7, 2026

Modelling transcription with explainable AI uncovers context-specific epigenetic gene regulation at promoters and gene bodies Author summary Genes are turned on or off through complex processes involving many proteins that interact with DNA wrapped histones and modify their structure. These changes, known as epigenetic modif...

🚀 Excited to share my latest paper on using SHAP, to predict direct target genes of chromatin-associated factors! Check it out for insights into gene regulation and the power of explainable AI in genomics! #XAI #SHAP #Genomics

doi.org/10.1371/jour...

Let's break down what we found! 👇

5/5 Many thanks to reviewers for their constructive feedback, and also to the editorial team of EMBO Journal for their availability and professionalism.

4/5 Overall, our results uncover an unexpected role for TET proteins in controlling early germline commitment. However, the molecular mechanisms underlying this phenomenon (which may involve targeted DNA de-methylation or other chromatin changes) remain to be investigated in further details.

3/5 Comparing single and combined TET1/2/3 knockout cell lines, we determined that redundant activity of TET1 and TET2 (but not TET3) controls stem cell differentiation potential. Additionally, we showed that TETs are dispensable for transitions between naïve, formative and primed pluripotent states

2/5 Our main finding is that TET proteins control the balance of differentiation between somatic and germline lineages. We found out that TET-deficient embryonic stem cells differentiate very efficiently into germ cells (PGCLCs) in vitro, at the expense of endoderm/mesoderm/ectoderm pathways.

TET knockout cells transit between pluripotent states and exhibit precocious germline entry | The EMBO Journal imageimageThe roles of TET DNA demethylases during early development remain poorly defined. This work uncovers independence of early mouse embryonic stem cell (ESC) transitions from TET proteins but a...

1/5 Glad to share our latest work with Ian Chambers’ lab published @embojournal.org in which we investigated the role of TET DNA de-methylases during cell fate transitions.
Great team effort, many thanks to Sara Gonzalez Brito @ebarbieri.bsky.social @edinuni-irr.bsky.social

doi.org/10.1038/s443...

TET knockout cells transit between pluripotent states and exhibit precocious germline entry
Ian Chambers and collaborators
www.embopress.org/doi/full/10....

TriRhena Gene Regulation Club The TriRhena Gene Regulation Club is a one-day symposium that brings together researchers from France (IGBMC), Germany (MPI-IE) and Switzerland (FMI) who share a common interest in gene regulation.

👉 The next TriRhena Gene Regulation Club takes place at the Friedrich Miescher Institute @fmiscience.bsky.social in Basel.

📅 Nov. 5th, 2025 (14:00-20:00)
📌 FMI, Basel
✍️ Registration deadline: Oct. 20th, 2025

Attendance is free 💸 , but registration mandatory:
www.ie-freiburg.mpg.de/gene-regulat...

Could I be added to the list as well? Thanks Alexis :)

Affinity-ligand purification of native human low-abundance multi-protein complexes for structure determination In human cells, large multi-protein transcription co-activators, such as chromatin remodelers or histone acetyltransferases, play critical roles in gene-expression regulation and are often implicated ...

Check out our new collaborative preprint about Affinity-ligand purification of native human low-abundance multi-protein complexes doi.org/10.1101/2025...

TET knockout cells transit between pluripotent states and exhibit precocious germline entry - preLights Genetic gatekeepers of gametogenesis? TET proteins jointly jam germline specification, synergistically steering cells towards somatic fates.

Genetic gatekeepers of gametogenesis? TET proteins jointly jam germline specification, synergistically steering cells towards somatic fates.

@justingutbio.bsky.social's new #preLight talks about the work of @r-pantier.bsky.social and the team. Have a look!

TET knockout cells transit between pluripotent states and exhibit precocious germline entry - preLights Genetic gatekeepers of gametogenesis? TET proteins jointly jam germline specification, synergistically steering cells towards somatic fates.

Excited to announce I recently highlighted another preprint for @prelights.bsky.social. In this preprint, @r-pantier.bsky.social and co-authors from the Chambers Lab at the University of Edinburgh find that the TET proteins act together to help mammalian cells specify into somatic lineages.

The human proteome with direct physical access to DNA Zero-distance photo-crosslinking reveals direct protein-DNA interactions in living cells, enabling quantitative analysis of the DNA-interacting proteome on a timescale of minutes with single-amino-aci...

Excited our paper is out in Cell @cp-cell.bsky.social!
🧬⚡ DNA photo-crosslinking proteomics in living cells
🎯 Pinpoints protein-DNA interactions to single amino acids
🌎 Globally quantifies DNA binding for >1800 proteins at a timescale of minutes
🔗 www.cell.com/cell/fulltex...
🧵

🚨 New preprint out! Do you think Single Molecule Footprinting and Fiber-seq are super cool but aren't sure how to unlock their full potential? HiddenFoot can help you: www.biorxiv.org/content/10.1...

Low overlap of transcription factor DNA binding and regulatory targets - Nature A near-complete survey of transcription factor activities in Saccharomyces cerevisiae reveals that most transcription factors have both activator and repressor activities and limited overlap between their binding sites on DNA and regulation of nearby genes.

Nature research paper: Low overlap of transcription factor DNA binding and regulatory targets

https://go.nature.com/4jedGUz

Call For Two Group Leader Positions - Strasbourg-Ville, Bas-Rhin (FR) job with IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) | 12837602 The Institute of Genetics, Molecular and Cellular Biology (IGBMC) is seeking two outstanding group leaders to establish independent research teams.

🚨3 weeks left to apply!🚨
We’re hiring 2 new Group Leaders at IGBMC – early career researchers welcome
🌟 We offer salary support for up to 3 years while you secure a permanent position in the French system.
Come join an international research environment in Strasbourg!
www.nature.com/naturecareer...

Hey! Check out our latest publication. A great collaboration with @longchrom.bsky.social and a nice example of how a negative result, the absence of a response to a transcriptional perturbation, can actually reveal an intriguing gene-specific buffering mechanism.
www.science.org/doi/10.1126/...