Data. A mouse model of glioblastoma leads to inevitable death within 50 days. Delivery of HSV+TK plus IL2, driven by a strong and specific synthetic superenhancer, allows almost all mice to survive even after nearly 150 days. From Fig5 of Koeber et al 2026
Just look at this graph (Fig 5A,B from Koeber et al).
Amazing.
Congratulations to the Pollard lab and all authors.
www.nature.com/articles/s41...
Excited to share our structural insights into how microtubules differentially guide phosphorylation of kinetochore-microtubule regulators, Ndc80 and MCAK, for chromosome segregation. Heroic efforts by Yiming Niu with a fun collaboration with Jennifer DeLuca lab!
www.science.org/doi/10.1126/...
Within the field of transcription, the distinctive style of Mark Ptashne and Kevin Struhl stands out.
At his best, Kevin Struhl provides a valuable clarification of the relationship between promoters and enhancers in the regulation of transcription.
www.annualreviews.org/content/jour...
Model of the C. elegans condensin I(DC) complex
Our new preprint in collaboration with @meisterpeterf.bsky.social uncovers the molecular basis for condensin recruitment to X chromosomes in C. elegans and reveals atomic-level details of a previously unknown auto-inhibited state of condensin.
www.biorxiv.org/cgi/content/short/2026.03.13.711519v1
Proud to share the yeast telomerase structure, led by the talented @hongmiaohu.bsky.social in collaboration with the Wellinger and Chartrand labs. Discovered 37 years ago and took us nearly 7 years but totally worth the wait 😍.
www.science.org/doi/10.1126/...
www.youtube.com/watch?v=gFE4...
Supercoiling not only brings DNA to life (and makes it dance) but also changes how key proteins such as #CRISPR interact with it. Thanks @qmsmith.bsky.social for the brilliant collaboration, Sylvia for developing an amazing new #imageanalysis pipeline & @eddierollins.bsky.social for beautiful #AFM.
New preprint from our lab! An H3.3 knockout does two things at once: it removes H3.3 from chromatin and destabilizes DAXX. We disentangle those functions and find that DAXX-mediated H3.3 deposition can be uncoupled from ERV silencing.
www.biorxiv.org/content/10.6...
These separation-of-function mutants show that H3.3 deposition can be genetically uncoupled from ERV silencing. This supports our earlier finding that H3.3 deposition at ERVs is dispensable for repression. Instead, repression depends on the C-terminal SIM and interaction with SUMOylated effectors.
Which DAXX functions are required for ERV silencing? DAXX mutants defective in ATRX binding or H3.3 deposition still restore ERV repression. By contrast, deletion of the C terminal SIM abolishes silencing. Thus, ERV repression requires the C terminal SIM, but not ATRX binding or H3.3 deposition.
One SUMOylated protein that binds the DAXX C-terminal SIM is the ATPase MORC3. Removing the SIM abolishes the DAXX-MORC3 interaction and prevents MORC3 recruitment to ERVs. MORC3 knockout cells likewise lose H3.3 accumulation at these loci.
We previously showed that the DAXX HBD alone is insufficient for H3.3 deposition. Deleting the final eight amino acids, which removes the C-terminal SIM, blocks H3.3 accumulation at ERVs without affecting DAXX localization.
Previously, we demonstrated that the DAXX four-helix bundle mediates ATRX interaction. But point mutations in this domain, or deletion of it, do not disrupt DAXX binding to ERVs or H3.3 accumulation at these sites.
The HBD basic patch is required for productive nucleosome assembly in vitro. In cells, basic patch mutants still localize to ERVs but do not restore H3.3 accumulation at those sites.
We identified a conserved basic patch within the tower domain of the DAXX histone-binding domain. Using recombinant HBD-H3.3-H4 complexes, we found that mutation of this surface weakened interaction with DNA in vitro.
In our study, we asked how DAXX promotes H3.3 deposition mechanistically. Genome-wide, DAXX is not widely distributed across repeats. It is concentrated at a restricted subset of evolutionarily young ERVK elements, where it restrains ERV expression and influences nearby genes.
A major challenge in interpreting H3.3 knockout phenotypes is that loss of H3.3 affects more than chromatin incorporation. It also causes a marked drop in DAXX abundance. Thus, ERV derepression in H3.3-null cells could reflect loss of H3.3 nucleosome assembly, loss of DAXX, or both.
New preprint from our lab! An H3.3 knockout does two things at once: it removes H3.3 from chromatin and destabilizes DAXX. We disentangle those functions and find that DAXX-mediated H3.3 deposition can be uncoupled from ERV silencing.
www.biorxiv.org/content/10.6...
Polycomb repressive-deubiquitinase complex safeguards oocyte epigenome and female fertility by restraining Polycomb activity www.nature.com/articles/s4...
The paper closes with a model: Gcn5-containing HAT complexes are targeted to active genes by the transcription machinery, providing a direct link between histone acetylation and gene activation. A fitting paper to revisit 30 years later, on what would have been Dave Allis's 75th birthday, March 22.
And then decisive experiment. Recombinant Gcn5p expressed in E. coli had HAT activity in the in-gel assay, whereas uninduced and vector-only controls lacked activity. With that, Gcn5p was assigned a direct biochemical activity, linking histone acetylation more directly to transcriptional activation.
The conceptual surprise was in the sequence. Tetrahymena p55 turned out to be highly homologous to yeast Gcn5p, a known transcriptional co-activator: ~40% identity, ~60% similarity, with a conserved bromodomain.
Then came the validation. Anti-peptide antibodies detected a single 55 kDa species, tracked with the active RP-HPLC fractions, and immunodepleted ~60% of HAT activity. p55 was not just associated with HAT A. It was the catalytic subunit.
Starting from the previously purified active p55 HAT A subunit, Brownell et al. sequenced six internal peptides, designed degenerate primers, and assembled the cDNA by PCR and RACE. The predicted protein sequence then recovered all six peptides from the purified enzyme.
Happy 30th birthday to this paper published March 22, 1996, one of the studies that moved chromatin biology from correlation toward mechanism. Brownell et al. linked a transcription-associated Tetrahymena HAT to yeast Gcn5p, providing a biochemical link for chromatin modification to gene activation.
Just out! 👀 for TFs that regulate TEs.Clara's work with @tamas-schauer.bsky.social @marliesoomen.bsky.social @palmrinmoy.bsky.social and bluesky-less lab members 🌎 identifies TBP as a regulator of specific ERVL class: MaLRs in 🐭embryos -as always -feedback welcome👍
link.springer.com/article/10.1...
How to make a heterochromatin by major satellite repeats transcripts?
www.nature.com/articles/s41...
1/ 🧵 In our new paper, we show that JARID2 and PALI1 mimic H3K27me3 to antagonise PRC2. www.cell.com/molecular-ce...
🧵 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...
Nice structural and biochemical dissection of how ATRX engages nucleosomes and couples ATP hydrolysis to productive sliding via a distinctive mechanism. www.biorxiv.org/content/10.6...
