This research represents a collaborative effort between several labs: Petra Hajkova, Juanma Vaquerizas and Mikhail Spivakov. My deepest thanks go to all our co-authors and amazing colleagues; I feel incredibly fortunate to collaborate with such a talented and dedicated group of people.
Thanks!
A special shout-out to my co-first author, Maria Rigua, @maria-rigau.bsky.social for her incredible partnership throughout this journey. I couldn't have navigated the twists and turns of this research without her.
How is transcription modulated in primordial germ cells when topologically associating domains (TADs) become attenuated?
Is centromere anchoring at the nuclear envelope the initial step that precedes telomere tethering?
What regulatory pathways control the enhanced deposition of CENPA once germ cells migrate into the gonads?
This work provides evidence to revise the current model of telomere tethering, at least in mice, and raises many interesting questions:
What other mechanisms ensure that the centromere is anchored at the nuclear periphery after each mitosis, and is this through passive or active regulation?
Happy to share our latest paper.
Our findings uncover a unique chromatin architecture and spatial chromosome arrangement in gonadal germ cells and document that alongside global DNA demethylation, the germline epigenetic reprogramming involves reorganisation of the 3D genome.
Congratulations!
5/ Marthe Gautier played a crucial role in identifying trisomy 21 as the cause of Down syndrome.
Working with minimal institutional support, she built a cytogenetics laboratory from scratch and produced the preparations that revealed an extra chromosome in affected children.
Nature has retracted a paper after an investigation at a U.K. institution found the first author — then a doctoral student — manipulated data.
Thanks!
Here is a copy of last year's Twitter thread explaining our preprint - jump to (21) for the new stuff 👀
Synergy between cis-regulatory elements can render cohesin dispensable for distal enhancer function
now revised and journal accepted at www.science.org/doi/10.1126/...
🧵👇
It’s been a while since I showed you the data.😂
I would like to thank Petra, Juanma and all authors, especially Maria Rigau who did the Hi-c analysis. To all lab members, thank you for your input and help to make this manuscript better.
This study raises a lot of interesting questions. Please read more about it in the manuscript and get in touch if you are interested. Happy to discuss.
Preprint: Global re-organisation of genome architecture at the transition to gametogenesis
In summary, our findings reveal a striking genome architecture remodeling that occurs at the transition to gametogenesis in mitotic PGCs, offering a unique model for physiological rewiring of 3D genome organization during epigenetic reprogramming in vivo.
9/9
The interesting observation does not stop here.
We also detect a striking loss of TAD boundaries and loop formation in PGCs, comparison with somatic cells. We think this is linked to lower expression of CTCF in germ cells. However, the molecular mechanism remains to be investigated. 8/9
What about global 3D genome organisation during this critical stage of germline development?
Consistent with our cytological observations, inter-chromosomal interactions were markedly reduced in both male and female PGCs, compared to somatic cells. 7/9
What is the potential mechanism for centromere anchoring in germ cells?
We show
1. H3K9me3 exhibited enrichment primarily around the nuclear periphery in PGCs.
2. Inhibition of H3K9 methyltransferase resulted in dislocation of centromeres.
6/9
IF combined with 3D telomere DNA FISH revealed a significantly higher number of telomere foci in PGCs compared to somatic cells.
The data support a model in which one end of the chromosome is tethered at the nuclear periphery, while the distal telomere is positioned inside the nucleoplasm. 5/9
The peripheral distribution of centromeres in PGCs is apparent in 3D reconstruction of confocal images. The data suggest that centromeres are separated in PGCs.
Surprisingly, despite the de-clustering of centromeres, the signal in the individual CENPA foci seemed more pronounced in PGCs. 4/9
Firstly, we tried to identify the localisation of chromosome ends. We observed an interesting distribution of centromeres in PGCs. Centromere foci were positioned close to the nuclear periphery with few attached to nucleoli near the periphery in both male and female germ cells. 3/9
So, what about nuclear architecture? Just by DAPI staining, you can easily distinguish between embryonic germ cells (dash line) and surrounding somatic cells (yellow arrow head).
It is more obvious if we use TEM. PGCs exhibit overall less electron-dense, dispersed chromatin state. 2/9
The germ cells are undergoing an extensive process called epigenetic reprogramming. It’s like hitting 'reset' button on the cell's memory. This reprogramming process involves global DNA demethylation, changes in nuclear morphology as well as remodeling of repressive histone modifications. 1/9
Happy to share our latest preprint.
We uncover a previously uncharacterised and evolutionarily conserved chromatin architecture in premeiotic gonadal germ cells, revealed through integrated cytological and high-resolution Hi-C approaches.
www.biorxiv.org/content/10.1...
Thread🧵🔽
Same feeling. Same…
[3] Navigating the pitfalls of mapping DNA and RNA modifications www.nature.com/articles/s41... [*] Please note the detection of exogeneous DNA mods is different from mapping natural endogenous DNA mods , because abundant exogeneous DNA mods are introduced (e.g. Fiber-seq, DiMeLo-seq, etc) n/n [END]
I believe that over the past ~ two decades, since the breakthrough papers on UHRF1, this is the first reported DNA methylation phenotype of its close paralog, UHRF2 (and not for lack of trying). Congrats to Ambre Bender and Michael Weber on this fantastic study! www.nature.com/articles/s41...
Reading published results is like looking at the distant star-everything you see happened in the deep past. Light years between a truly novel discovery and its communication within the scientific community.
Finally out! 🥳 Our paper showing how a transposable element (TE) insertion can cause developmental phenotypes is now published @natgenet.nature.com 🧬🦠🐁
Below is a brief description of the major findings. Check the full version of the paper for more details: www.nature.com/articles/s41588-025-02248-5
