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Genomic and epigenomic regulation of cell fate

Genomic and epigenomic regulation of cell fate

DEPARTMENT

Functional genomics and cancer

TEAM LEADER

Raphael PANTIER

DNA is packaged in the form of “chromatin” including nucleosomes, epigenetic modifications and a large number of proteins associated with various biological processes. Chromatin regulators allow genetic information to be decoded differently depending on cellular context. In this way, unique gene expression programs are activated in each cell type, leading to distinct phenotypes and specialised functions.

How is cellular identity regulated during developmental processes, or disrupted in pathological conditions? In our laboratory, we aim to address this fundamental question using cutting-edge genetic engineering, biochemical assays and high-throughput sequencing technologies. In particular, our research focuses on transcription factors and epigenetic regulators, which are critical for embryonic development and often de-regulated in human diseases such as cancer and neurodevelopmental disorders.

We take advantage of mouse embryonic stem cells as a model system for cell fate decisions. Using genetically manipulated pluripotent cells, we can assess not only the influence of proteins of interest on the transcriptome and epigenome, but also test their phenotypic impact on cellular differentiation in vitro and embryonic development in vivo.

 

Cell fate and chromatin

Members

Researchers

Post-doctoral fellows

PhD students

Technicians

Current projects

Deciphering the principles of gene regulation by the atypical transcription factor SALL4 (AT-BASE)

Our recent work demonstrated that the stem cell factor SALL4 controls transcription in proportion to the A/T nucleotide content of its target genes. This project aims at uncovering the molecular mechanisms underlying this new mode of gene regulation at three different genomic scales:

  • Enhancers: regulation of transcription initiation via long-range looping with promoters of target genes?
  • Gene bodies: regulation of transcription elongation via local binding of SALL4 over gene units?
  • Lamina-associated domains: regulation of 3D genome architecture via dispersed binding of SALL4 over the AT-rich genome?

AT-BASE (EN)

Relevant publications:

1- Pervasive Binding of the Stem Cell Transcription Factor SALL4 Shapes the Chromatin Landscape. Chhatbar, K.; Giuliani, S.; Quante, T.; Alexander-Howden, B.; Selfridge, J.; Guy, J.; Auchynnikava, T.; Spanos, C.; Mathieson, T.; Sanguinetti, G.; Bird, A.; Pantier, R. bioRxiv (preprint), 2025. https://doi.org/10.1101/2025.11.14.688441

2- Tetramerisation governs SALL transcription factor function in development and disease. S. Giuliani, K. Chhatbar, M. Wear, J. Guy, T. Mathieson, H. Burdett, L. George, G. Alston, C. Spanos, T. McHugh, D. Kelly, R. Pantier and A. Bird. bioRxiv (preprint), 2025. https://doi.org/10.1101/2025.10.27.684836

3- Structure of SALL4 zinc finger domain reveals link between AT-rich DNA binding and Okihiro syndrome. J.A. Watson, R. Pantier, U. Jayachandran, K. Chhatbar, B. Alexander-Howden, V. Kruusvee, M. Prendecki, A. Bird, A.G. Cook. Life Science Alliance, 2023. https://doi.org/10.26508/lsa.202201588

4- High-throughput sequencing SELEX for the determination of DNA-binding protein specificities in vitro. R. Pantier, K. Chhatbar, G. Alston, H.Y. Lee, A. Bird. STAR Protocols, 2022. https://doi.org/10.1016/j.xpro.2022.101490

5- SALL4 controls cell fate in response to DNA base composition. R. Pantier, K. Chhatbar, T. Quante, K. Skourti-Stathaki, J. Cholewa-Waclaw, G. Alston, B. Alexander-Howden, H.Y. Lee, A.G. Cook, C.G. Spruijt, M. Vermeulen, J. Selfridge, A. Bird. Molecular Cell, 2021. https://doi.org/10.1016/j.molcel.2020.11.046

Funding and partners

- 2026: “Tremplin ERC” funding (T-ERC) – French National Research Agency (ANR)

- 2025: Young Researchers program (JCJC) – French National Research Agency (ANR)

- 2025: “Attractivity” Excellence initiative (IdEx) – University of Strasbourg

- 2025: Excellence laboratory (LabEx) Startup package – IGBMC

ANR                 France 2030                Universite de Strasbourg                

Publications