Happy to share that David and I have a new review out in @annualreviews.bsky.social of Biochemistry!
We break down Pol II pausing, its evidence in vitro/in vivo, and its two key fates which are in kinetic competition: pause release vs premature termination.
www.annualreviews.org/content/jour...
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...
🧵 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...
Incredibly proud to share our new preprint, lead by the Incomparable Rithika Sankar.
Here we temporally dissect the role of FACT in mES cells, finding that FACT loss drives progressive deterioration of chromatin architecture, leading to transcriptional collapse.
www.biorxiv.org/content/10.6...
I am excited to share a new review @cp-molcell.bsky.social written in collaboration with @tanjamittag.bsky.social , Mikayla Eppert, and Ambuja Navalkar where we review the current evidence for and against the role of density transitions in regulating transcription www.cell.com/molecular-ce...
Great work by postdoc Francisco Perez de los Santos in my lab, with past/present crew, esp. GS Lily Beck. Thanks to collaborators Kim Jordan, Matt Taylor, and others. Dedicated to Charles, who would have loved to see the final product.
When the project started, we thought the variant was quite rare, but it turns out EZH2-L50S is present at 1 in ~10-20K individuals, suggesting wider impact.
With purified PRC2, we showed that L50S reduces the ability to methylate nucleosomes and disrupts allosteric stimulation by methylated peptides. This defect likely contributes to erosion of proper gene expression in B cells in patients.
@4everbiochemist.bsky.social helped us fire up CUT&Tag, which highlighted that loci with high WT H3K27me3 were most depleted in L50S. Surprisingly, EZH2-L50S protein recruitment is higher than WT at these sites—potentially stuck.
Patient samples were low on B cells, so we modeled this mutation in 293 cells to understand fundamentally how EZH2 may be affected. H3K27me3 (heterochromatin mark catalyzed by EZH2) trended down in cells, but which loci were affected?
Patients had Common Variable Immunodeficiency (CVID), low Ig and low B cells, esp. memory, all occurring in adulthood, leading to increased infections. Sequencing ID’d EZH2-L50S as a shared variant. EZH2 is in demand by B cells in adulthood, for differentiation and maturation.
Model figure showing EZH2-L50S effect on chromatin and B cell gene expression from https://www.biorxiv.org/content/10.64898/2025.12.08.692979v2.article-metrics.
Updates after feedback, so now’s the time to advertise! Our work with the late, great Charles Kirkpatrick, a force in Clin. Immunology for 60 yrs. We found that B cell immunodeficient patients of his had a hypomorphic variant in EZH2 caused by a defect in allostery. www.biorxiv.org/content/10.6...
new paper from the Lai lab! Renfu Shang performs careful mechanistic dissection of miRNA cluster assistance and reveals many insights and surprises to this enigmatic regulatory strategy that gives suboptimal miRNAs a boost. if you love Northerns, you'll ♥️ this! 🧬
genesdev.cshlp.org/content/earl...
Happy to announce the publication of our foray into studying what happens to the transcriptomes of nuclei when cells fuse to form a syncytium. More to follow in the coming few years.
One really wonderful thing about the Company of Biologists is that's it's free to publish there for my university!
The Reck-Peterson lab at Weill Cornell Medicine is seeking a technician or staff scientist to work on Aspergillus projects. Broad background in fungal biology and techniques required. Bioinformatics skills preferred. Find out more at: reckpetersonlab.org.
Our study with @stadtfeldlab.bsky.social on the dual mechanism by which EHMT2 is repressing totipotency-associated vs lineage-specific loci is now out @emboreports.org. See thread by @cmuyehara.bsky.social who led the study with K Chatterjee. Full article here link.springer.com/article/10.1...
Very happy to share our paper rdcu.be/eUImj out today in @natcellbio.nature.com 🎉🎉🎉
We uncover an unexpected role for endogenous Xist RNA in regulating X-linked genes that escape X-inactivation.
Excited to share that this work is now published in its final form!
link.springer.com/article/10.1...
Took us a bit, but proud of this published version. We now examine the genetic interaction of phosphorylation with oligomerization and where bulk and phospho-Swi6 localize. Wonder if chromatin affinity tuning to enable Suv39 H3K9me3 spreading is a conserved mechanism ?
doi.org/10.1093/nar/...
Absolutely thrilled to share the latest work from my lab focused on the variation and evolution of human centromeres among global populations! We assembled 2,110 human centromeres, identifying 226 new major haplotypes and 1,870 α-satellite HOR variants. www.biorxiv.org/content/10.6...
@pravrutharaman.bsky.social got super intrigued about EZHIP/CATACOMB, previously identified as a histone H3K27M mimic of PRC2. You can read about her efforts here: www.biorxiv.org/content/10.6... We hope these analyses will help spur more analyses in this very cool gene! 1/
Known for decades: DNA sequence drives nucleosome "rotational positioning" (which face of DNA contacts histones)
But: How does this persist when remodelers & transcription constantly mobilize nucleosomes? Our new preprint 1/ :
www.biorxiv.org/content/10.6...
The Gonzalez Lab at Columbia University is seeking a scientific leader!
Join us in a Research Scientist position, driving single-molecule, structural, and biochemical studies of translation, translational control, and other RNA-based processes.
Apply: apply.interfolio.com/176949
How does a “universal” transcription factor evolve to do species-specific jobs?
Our new preprint reveals how divergence in TBP’s domains shapes transcriptional specialization across eukaryotes.
Read it here 👉
www.biorxiv.org/content/10.1...
#MolecularEvolution #Transcription
Some (+)ve news to lighten another heavy weekend: our latest preprint (c/o Mattiroli + Ramani labs) is up!
www.biorxiv.org/content/10.1...
A tour-de-force by 1st authors Bruna Eckhardt & @palindromephd.bsky.social, focusing on chromatin replication. RTs welcome; tweetorial in 3,2...(1/n)
Our paper is out in its final form! Back in April 2023, my coauthor Aleks Radakovic, then a PhD student, approached me after a talk in Chicago to ask what I thought an aminoacylated tRNA would look like if we pulled it through a @nanopore.
doi.org/10.1038/s414...
if i were a better person i would do a tweetorial on our recent paper - but, hey, read the paper. its right there, waiting for you. #Giantvirus #histones are cool! their #nucleosomes are cool. check it out.! thats the tweetorial.
rdcu.be/exXBX
