iiinova — where your digital self keeps evolving

Thomas Schalch @schalchlab.bsky.social · 04/03/2026

Special mention to @ammaraht.bsky.social, whose dedication to this project was instrumental to getting it here. Thanks to everyone across Leicester, FMI Basel, UCL and Geneva who contributed along the way. www.biorxiv.org/content/10.6...

biorxiv.org

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Thomas Schalch @schalchlab.bsky.social · 04/03/2026

AlphaFold models of the human RNF20/RNF40 and S. cerevisiae Bre1 complexes show the same priming rearrangement, with conserved RBR residues. This looks like a universal activation mechanism for Bre1-type E3 ligases.

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Thomas Schalch @schalchlab.bsky.social · 04/03/2026

The interface is a short region in the HMD domain we call the RBR. Systematic mutagenesis in S. pombe produces accurately what the model predicts and is supported by the biochemistry.

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Thomas Schalch @schalchlab.bsky.social · 04/03/2026

The key finding: when we model HULC together with the HMD domain of Prf1, the RING domains and Rhp6 snap into a catalytically primed configuration. Without Prf1, the RMSD versus a known primed RING-E2-Ub structure is ~32 Å. With Prf1, it drops to 1.2 Å.

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Thomas Schalch @schalchlab.bsky.social · 04/03/2026

HULC is a 1:1:1:1 assembly (Brl1-Brl2-Rhp6-Shf1) built around an elongated coiled-coil hairpin. Shf1 is structurally integral to the hairpin—not peripheral. The complex is flexible, with its catalytic modules loosely tethered and poorly configured for ubiquitin transfer on their own.

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Thomas Schalch @schalchlab.bsky.social · 04/03/2026

H2Bub is deposited by the HULC complex, recruited to RNA Pol II via PAF1C. But how PAF1C activates HULC has been unclear. We used AlphaFold modelling, biochemical reconstitution, XL-MS, SAXS and cryo-EM to find out.

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Thomas Schalch @schalchlab.bsky.social · 04/03/2026

🧵 New preprint from our group, in collaboration with the @marcbuhler.bsky.social lab at FMI Basel and the Thalassinos lab at UCL. A long project and a finding we're really pleased with. Thread 👇 www.biorxiv.org/content/10.6...

biorxiv.org

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Thomas Schalch @schalchlab.bsky.social · 07/01/2026

Congratulations to the Chloe Hall and the Chaplin group! We're very proud to be part of this fantastic effort to produce structures of NHEJ assemblies on nucleosomes. This brings us closer to understanding how DNA repair machinery deals with a chromatin substrate: www.nature.com/articles/s41...

nature.com

Cryo-EM structures of NHEJ assemblies with nucleosomes - Nature Communications

DNA double-strand breaks endanger genome stability. Here, the authors present cryo-EM structures showing how Ku70/80 and DNA-PK bind DNA ends on nucleosomes, offering a mechanistic model for break rec...

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Reposted by Thomas Schalch

Rob Schneider @robertife.bsky.social · 23/01/2025

Please RS/RT. #GordonConference "Histone and DNA Modifications" Program is now online 🍾 #epigenetics #chromatin #histones 20.-25. July. Il Ciocco 🇮🇹 Register now: ➡️ shorturl.at/AtAjz Exciting speaker lineup, many slots for talks selected from abstracts

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Reposted by Thomas Schalch

Karsten Rippe @karsten-rippe.bsky.social · 13/12/2024

🧬 1/ Heterochromatin protein 1 (HP1) still surprises us after all these years: It simply sticks to chromatin when pericentric heterochromatin domains – the chromocenters – are activated in mouse fibroblasts and acts as a local rather than global repressor. New preprint: doi.org/10.1101/2024...

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Reposted by Thomas Schalch

Qi Zhang @qizhang85.bsky.social · 10/12/2024

I am recruiting a postdoc with experience in Protein Biochemistry, Structural Biology & Chromatin Biology. If you are passionate about the complex world of chromatin modifications, please contact me for more details 🙏. Location: SAiGENCI, Adelaide, Australia 🦘🍷🏄🏖️🇦🇺

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Reposted by Thomas Schalch

Michael Tellier @michaeltellier.bsky.social · 21/11/2024

We have an exciting and multidisciplinary fully-funded BBSRC MIBTP #PhD position between my lab and Massimo Cavallaro's lab coupling genomics, transcriptomics, and mathematical modelling to investigate the regulation of gene expression. Deadline: 16th January 2025. www.findaphd.com/phds/project...

findaphd.com

Unravelling age-related gene expression dysregulation through system biology and mathematical modelling. at University of Leicester on FindAPhD.com

PhD Project - Unravelling age-related gene expression dysregulation through system biology and mathematical modelling. at University of Leicester, listed on FindAPhD.com

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Thomas Schalch @schalchlab.bsky.social · 18/11/2024

Gutting when you find your dream project done and dusted on bioRxiv. Du et al. performed an impressive tour-de-force to solve the Clr4-H3K14ub structure. Great to see that the ubiquitin-binding region we found by XDS-MS matches the crystal structure perfectly! www.biorxiv.org/content/10.1...

biorxiv.org

Mechanistic Insights into the Stimulation of the Histone H3K9 Methyltransferase Clr4 by Proximal H3K14 Ubiquitination

H3K9 methylation is an evolutionarily conserved hallmark of heterochromatin and plays crucial roles in chromosome segregation, genome stability, and gene expression regulation. Clr4 is the sole histon...

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Reposted by Thomas Schalch

Jackson Hoffman @jxhoffman.bsky.social · 10/11/2024

Putting together packs of transcription and Chromatin people - Nominate others to add! go.bsky.app/5zgpZfg

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