Thank you @anajaneva.bsky.social for sharing our work. You and IES are deeply missed! ❤️

Read the press release on our work from
@www.helmholtz-munich.de here:
www.helmholtz-munich.de/en/epigeneti...

It has been an incredible journey in the @epihmgu.bsky.social community, with lots of discussions and advice. Also thanks to everyone who provided plasmid constructs for designing the screen and help with sequencing!

Grateful to all co-authors and collaborators who contributed their expertise, especially during the revisions! 🙏Thank you @mamartirenom.bsky.social for your guidance with the meta-analysis of the huge dataset.

🧬 This work is the result of a lot of hard work over 5 years of my PhD.

Huge thanks to @metorrespadilla.bsky.social for trusting me with this challenging opportunity. Special mention to my bioinformatics buddy and plot wizard @tamas-schauer.bsky.social

n/n✨ In summary:
LAD formation is epigenetically regulated, developmentally staged, and remarkably resilient!

9/n: Successful zygotic genome activation (ZGA) is typically associated with correct nuclear-lamina organization...

...but ZGA can occur even when lamina contacts are perturbed, especially at the resilient 2-cell stage.

8/n: Early embryos lack the constitutive heterochromatin pathway, including chromatin-compacting histone variants.

This absence enables the non-canonical embryonic chromatin to co-exist with a unique and dynamic LAD organization not seen in differentiated cells.

7/n: We found that compartment boundaries constrain LAD disruption and serve as scaffolding cues for organizing the genome.

LADs often spread only within B compartments, and LAD inversions follow compartment boundaries.

6/n:🧬 Even if LADs are disrupted in zygotes, embryos can rebuild LAD architecture at the 2-cell stage.

BUT:
Disruption at the 2-cell stage impairs preimplantation development.

5/n:🎯 H3K4me3 contributes to the robustness of nuclear organization.

HP1 proteins anchor broad H3K9me3 domains to the lamina. But H3K4me3 acts as a barrier, a chromatin boundary that blocks excessive lamina binding.
This balance is critical for correct nuclear organization.

4/n: We found that maternal inheritance of H3K27me3, not de novo methylation, is key to LAD formation in zygotes.

🎯 LAD establishment is maternally bookmarked and regulated through a PRC2–lamina antagonism.

3/n:💡 We discovered that chromatin pathways, not structural components, are the primary regulators of LADs in early embryos.

The interplay of H3K9, H3K27, and H3K4 methylation is a major player in shaping genome-lamina contacts.

2/n: Using in vivo perturbation screening + simultaneous LAD mapping, we built a toolbox to explore how chromatin dynamics guide nuclear organization post-fertilization.

🧬 A glimpse into the genome's first "address book" at the beginning of life.

1/n: We reveal how chromatin pathways shape genome-lamina interactions in early mouse embryos, and what happens when they go wrong.