iiinova — where your digital self keeps evolving

Reposted by Paul Batty

Davide Seruggia @dseruggia.bsky.social · 26/02/2026

Happy to share our paper in collaboration with cancerbits.bsky.social. We used machine learning & ATAC-seq to refine erythroid differentiation protocols. Recipes for lineage differentiation are written on chromatin! @stanna-ccri.bsky.social @cemm.oeaw.ac.at

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Reposted by Paul Batty

Gerlich Lab @gerlichlab.bsky.social · 25/02/2026

1/New preprint just dropped! 🔥🔥 We investigate how the genome is destroyed in apoptotic cells in a way that prevents DNA fragments from spreading beyond the dying cell 🧬⚰ Done here at @imbavienna.bsky.social & in the super @rcollepardo.bsky.social & Rosen labs: www.biorxiv.org/content/10.6...

biorxiv.org

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Reposted by Paul Batty

Gerlich Lab @gerlichlab.bsky.social · 03/09/2025

1/ New preprint alert! In collaboration between the Rosen, Redding, Collepardo-Guevara & Gerlich labs, we uncover a surprising principle of chromosome organisation: electrostatic repulsion positions centromeres at the chromosome surface during mitosis. 🔗 doi.org/10.1101/2025...

doi.org

An electrostatic repulsion model of centromere organisation

During cell division, chromosomes reorganise into compact bodies in which centromeres localise precisely at the chromatin surface to enable kinetochore-microtubule interactions essential for genome se...

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

This was a team effort so we would like to thank all coauthors for their contributions, our host institutions @stanna-ccri.bsky.social and @cemm.oeaw.ac.at , @fwf-at.bsky.social and @erc.europa.eu for funding and all members of the Seruggia lab for their feedback. Stay tuned for more!

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

In conclusion, we reveal a structural dependency within the SAGA CORE that regulates KAT2A protein stability, and define a degradation pathway that eliminates orphan KAT2A. These results provide insight into why CORE components might be vulnerabilities in cancer, such as AML and neuroblastoma. 9/n

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

Finally, we asked whether loss of TADA1 would lead to collateral loss of other SAGA components, including its co-translational assembly partner TAF12. Indeed, using TMT proteomics we detected progressive depletion of several TADA1 neighbours in the CORE and HAT modules, including TAF12. 8/n

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

We identified UBR5, an E3 ligase involved in orphan protein degradation, and OTUD5 as hits whose loss resulted in stabilisation of KAT2A when the SAGA CORE is disrupted, a result which we confirmed by immunofluorescence of endogenous KAT2A in both TAF5L KO and TADA1 KO cells. 7/n

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

We next wanted to know what mechanism is driving KAT2A protein loss. Since proteasome inhibition rescues KAT2A back to wild-type levels, we teamed up with Caroline Schaetz and @georgwinter.bsky.social to look for factors responsible for the degradation of non-complexed KAT2A. 6/n

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

To test this hypothesis, we turned to sucrose gradient fractionation. In TAF5L and TADA1 KO cells, KAT2A is lost accumulates in low molecular weight fractions, indicating that the HAT module dissociates from SAGA. Thanks to @supertifurgalab.bsky.social and Gabriel Onea for their help with this. 5/n

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

Intriguingly, in TAF5L KO cells residual KAT2A was not identified around its normal binding sites at promoters on chromatin, suggesting that the HAT module might have dissociated from SAGA. 4/n

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

We focused our validation on three CORE components, TAF5L, TAF6L, and TADA1. In KO clones we confirmed a ~50% reduction in KAT2A signal, which could be rescued by cDNA overexpression. Interestingly, this was sufficient to phenocopy KAT2A KO at the level of H3K9ac. 3/n

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

Using a fluorescent KAT2A stability reporter to monitor KAT2A abundancy upon KO of other members of SAGA, we found that loss of HAT and of specific CORE components results in a reduction in KAT2A protein abundance. 2/n

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Paul Batty @paulbatty1.bsky.social · 01/08/2025

I am pleased to share a new preprint from my postdoc in the @dseruggia.bsky.social lab. We discovered a structural dependency within the CORE module of the transcriptional coactivator SAGA, which regulates the stability of its histone acetyl transferase, KAT2A. www.biorxiv.org/content/10.1... 1/n

biorxiv.org

Disruption of the SAGA CORE triggers collateral degradation of KAT2A

The SAGA transcriptional co-activator complex regulates gene expression through histone acetylation at promoters, mediated by its histone acetyl transferase, KAT2A. While its structure and function ha...

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Reposted by Paul Batty

Anton Goloborodko @golobor.bsky.social · 15/07/2025

We found a new asymmetry in the large-scale chromosome structure: sister chromatids are systematically shifted by hundreds of kb in the 5′→3′ direction of their inherited strands! The work was led by Flavia Corsi, in close collaboration with the Daniel Gerlich lab. www.biorxiv.org/content/10.1... 1/

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