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.

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!

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...

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.

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