The Lewis Lab

Allosteric activation of PRC2 is coupled to adoption of the compact state. Our new bioRxiv manuscript shows that EZH2 S21-phos, adjacent to the SANT1 domain, restrains this conformational transition and limits activation. With @kasinath-lab.bsky.social & @garcialabms.bsky.social tinyurl.com/4369kmh2

(1/9) Excited to share my preprint on Polycomb 3D chromatin interactions from my postdoc with @andersshansen.bsky.social! We were surprised to find that canonical PRC1 doesn't seem to be the only contributor to these interactions: www.biorxiv.org/content/10.6...

How can histone acetyl-transferase acetylate a specific histone tail residue ? Using cryo-EM, we captured the MSL complex in a stable post-catalytic state, visualising the acetyl group on H4K16, a central mark for gene regulation authors.elsevier.com/sd/article/S...

Finally a more intuitaive way to learn pLDDT/pAE? 😎 sokrypton.github.io/protein_figh... (Character idea from @hannes-stark.bsky.social & Alex Waldherr)

Fold Spacer lets you fly through protein structures (Weekend project #2). It’s my first game: I originally set out to build a racer with structures as the tracks, but was a little too crazy. So it became this instead. You can upload your own structures. 🌐 martin-steinegger.github.io/Fold-Spacer/

New Online! PRC2–RNA interactions through the lens of bioinformatics pipeline choices

Really timely review by @camimoso.bsky.social and @adelmanlab.bsky.social on RNAP in metazoans. I really like the idea of a RNAP having to "mature" in order to become a productive transcriptional machine. Plus it has my #1 favorite snRNP involved... www.nature.com/articles/s41...

* Hot off the press from the Rowe Lab 📢 * : For in depth insight on LINE-1 jumping genes, from their regulation to their multifaceted roles in cancer immunity, read Holly Jefferson's review here: www.mdpi.com/1999-4915/18...

Preprint alert! 🚨 We are very excited to share our new manuscript on Bohring-Opitz syndrome, a devastating rare monogenic disorder driven by truncating variants in ASXL1. This project was led by PhD student Emma Doyle, one of the OG Conway lab members 💪. 1/6 www.biorxiv.org/content/10.6...

(2/2) www.nature.com/articles/s41...

Does every enhancer work with every promoter? With @jengreitz.bsky.social and Will Greenleaf, we revisit this long-debated question and resolve an outstanding contradiction in the field. A tour 🧵👇 www.biorxiv.org/content/10.6...

Independent of sequence, disordered regions promote the stable chromatin occupancy required for pioneer-factor activity www.science.org/doi/10.1126/...

Excited to share this preprint!! with @brandonscooper.bsky.social and Bill Sullivan We tested whether endosymbiotic Wolbachia can alter host gene expression through chromatin modifications that persist from spermatogenesis to adulthood.

‪doi: doi.org/10.1038/s414... 📣 Our study is now out in Nature Communications detailing that the type I interferon pathway is suppressed by HUSH in early human development: Its complete epigenetic lockdown!! Incredible work from James Holt 📣 😎

Sub-cellular architectures arise through integrating signaling and structure. @edenchang.bsky.social and @zjmaggiexu.bsky.social show how coupling reaction-diffusion signaling to protein condensation provides a tunable, regulatable landscape for sub-cellular structure www.biorxiv.org/content/10.6...

A strong hint from human genetics that changes in DNA methylation may be causal for normal aging. This is the direction that aging (and cancer) research needs to go! www.nature.com/articles/s41...

Our new Review is out now! @carolinedean.bsky.social @miguelmontez.bsky.social We discuss how plants monitor seasonal temperature exposure, highlighting interconnected mechanisms of short-term transcriptional regulation & long-term epigenetic memory rdcu.be/fnLmG 🌱❄️

Here is our article published in Nature Comm, on new players in chromatin dynamics after UV repair. This work highlights the histone chaperones DNAJC9 and MCM2 as central players in chromatin repair. Our proteomic dataset opens up new perspectives for dissecting epigenome maintenance mechanisms.

Yaay! Well done @bluebuleta.bsky.social and team! Great to see this work finally out! Read the paper to see how SETDB1 and HUSH regulate Xist transcription

We’ve recently been awarded a MIRA R35 and an R01 to study non-canonical roles and missense mutations of the Polycomb system in health, cancer, and neurodevelopmental disorders. We are seeking an animal tech with lab manager duties. Please share!

How do cells tune PRC2 allostery? We find EZH2 Ser21-phos restrains PRC2 adoption of the compact active state. Loss of this restraint promotes H3K27me3, redistributes cPRC1, and impairs differentiation. New bioRxiv with @kasinath-lab.bsky.social & @garcialabms.bsky.social! tinyurl.com/4369kmh2

Does PRC2 interact with RNA or is it an artefact? See our preprint showing how stringent denaturing purifications with spike-in controls support direct interaction between PRC2 and RNA in cells. www.biorxiv.org/content/10.6...

Out today - structure of the human HIRA histone chaperone complex bound to nucleosomes. Ever wondered how nucleosomes are assembled in the wake of transcription? It takes a 'hulk of a protein complex'. Work by the amazing Wei Tian weetian558.bsky.social. www.biorxiv.org/content/10.6... 🧵

Why can't we explain enhancer action despite 2 decades of chromosome conformation technologies? 😬 Our new study spearheaded by Leonid Mirny's group points to a flaw in our assumptions, and to a solution from physical principles By @timothyfoldes.bsky.social 💻& @karissalhansen.bsky.social 🧪 🧵👇

Is distal gene activation by enhancers inherently different from promoter-proximal activation? We propose not. But both cohesin and cooperativity are important aspects of how transcription is affected. Happy to share our recent preprint (thread below) 1/ www.biorxiv.org/content/10.6...

Delighted to share our lab's latest (w/ inimitable @genophoria.bsky.social) in final form at @nature.com. Enormous lift by Sean Wang, @palindromephd.bsky.social & @martyyang.bsky.social to address extensive & constructive reviewer comments & see this through. (1/n) www.nature.com/articles/s41...

In a genome not so far away, the most elegant design in the galaxy was already wrapped into ~147 base pairs. #HappyNucleosomeDay, May-The-Fourth Be With You.

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...

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.

Polycomb repressive-deubiquitinase complex safeguards oocyte epigenome and female fertility by restraining Polycomb activity www.nature.com/articles/s4...