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

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]

This is so important for the field.

Congratulations!