Chen Davidovich

We are excited to share our new preprint demonstrating that nucleic acid interactions with SUZ12 constrain PRC2 activity, establishing a kinetic buffer essential for targeted gene silencing and revealing vulnerabilities in diffuse midline gliomas.
www.biorxiv.org/content/10.1...

How do chromatin remodelers use #IDRs to find TF binding partners? In our new Molecular Cell paper, we show that β-catenin is an adaptor that links SWI/SNF (cBAF) subunit ARID1A with binding partners via IDR-domain interactions.
www.cell.com/molecular-ce...

Australian Cell Cycle, DNA repair and Telomere Meeting October 20-22, 2025

Register for the Australian Cell Cycle, DNA Repair & Telomere Meeting in beautiful Melbourne October 19-22, 2025. Plenty of slots for selected abstracts and posters. High praise last time from Piotr Sicinski: "en par with a Gordon conference for science and interaction"
www.australiancellcycle.org

Happy to announce a new preprint from my lab looking in to the establishment of polycomb domains in early fly development and contributions from pioneer factors Zelda and GAGA-factor.

✨Excited to share my first postdoc paper on chromatin remodeler, MORC2 ✨

Using #cryoEM & #singlemolecule imaging, we reveal how MORC2 compacts DNA 🔬🧬

Thanks to all collaborators from @wehi-research.bsky.social @ccemmp-outreach.bsky.social Uni Melb, Monash Uni, Seoul National Uni and Texas Uni!

Simultaneous epigenomic profiling and regulatory activity measurement using e2MPRA Cis-regulatory elements (CREs) have a major effect on phenotypes including disease. They are identified in a genome-wide manner by analyzing the binding of transcription factors (TFs), various co-fact...

Lentivirus massively parallel reporter assays integrate & enrich for specific sequences in the genome. We utilize this to test their epigenetic modifications & open chromatin alongside their regulatory activity. Amazing work by Zicong Zhang, Fumitaka Inoue & others.
www.biorxiv.org/content/10.1...

New from our lab & @harrisonflylab.bsky.social: Drosophila models of H3 K27M & EZHIP reveal conserved chromatin regulators that buffer PRC2 inhibition. An in vivo screen highlights how developmental defects can be rescued despite global H3K27me3 loss.
doi.org/10.1101/2025...

The human proteome with direct physical access to DNA Zero-distance photo-crosslinking reveals direct protein-DNA interactions in living cells, enabling quantitative analysis of the DNA-interacting proteome on a timescale of minutes with single-amino-aci...

Excited our paper is out in Cell @cp-cell.bsky.social!
🧬⚡ DNA photo-crosslinking proteomics in living cells
🎯 Pinpoints protein-DNA interactions to single amino acids
🌎 Globally quantifies DNA binding for >1800 proteins at a timescale of minutes
🔗 www.cell.com/cell/fulltex...
🧵

Now published! Big congrats to first author @gginell.bsky.social

We are actively working improving/updating various aspects of FINCHES; don't hesitate to reach out if you run into issues, have questions.
www.science.org/doi/10.1126/...

Single-molecule analysis reveals the mechanism of chromatin ubiquitylation by variant PRC1 complexes Single-molecule experiments show that active conformation formation controls chromatin ubiquitylation kinetics by variant PRC1.

Our new study of chromatin ubiquitylation by variant PRC1 on the single-molecule scale: We visualize directly how vPRC1 ubiquitylates neighboring nucleosomes during a single binding event, showing a potential mechanism how H2Aub domains are established.
www.science.org/doi/10.1126/...

Single-molecule analysis reveals the mechanism of chromatin ubiquitylation by variant PRC1 complexes Single-molecule experiments show that active conformation formation controls chromatin ubiquitylation kinetics by variant PRC1.

Check out our new study of chromatin ubiquitylation. @alexateslenko.bsky.social visualized directly at single molecule scale how vPRC1 ubiquitylates neighboring nucleosomes. These results suggest potential mechanism on how H2Aub domains are established. 👇👇👇
www.science.org/doi/10.1126/...

Check out this 🧵 from @eimearlagan.bsky.social on our new Molecular Cell @cp-molcell.bsky.social paper! We show how the H3K27M Oncohistone reprograms chromatin in DMG, creating a specific dependency on CBX4/PCGF4-containing forms of cPRC1 👇

Macromolecular interactions dictate Polycomb-mediated epigenetic repression The dynamic regulation of epigenetic states relies on complex macromolecular interactions. PRC2, the methyltransferase complex responsible for depositing H3K27me3, interacts with distinct accessory pr...

Excited to share a preprint from my lab on distinct specificity and functions of PRC2 subcomplexes: www.biorxiv.org/content/10.1...

Big thanks to @davidovichlab.bsky.social for sharing this toolkit! Check it out here: www.addgene.org/kits/davidovich-moclo-baculo/

I'm super excited to announce that registrations are now open for the 19th Australian Cell Cycle, DNA Repair and Telomere Workshop. Awesome international speaker line-up, with plenty of locals being invited! Book now to secure your earlybird rate. www.australiancellcycle.org

Big thanks to @addgene.bsky.social for making our MoClo Baculo available as a kit! All the plasmids for Golden Gate assembly of baculovirus vectors, now bundled together:
www.addgene.org/kits/davidov...
🧪🧬 #MolecularCloning #baculovirus #ProteinExpression


🧬🎉Thrilled to share our new chromatin remodeling study! We reveal three states of human CHD1 and identify a novel "anchor element" that interacts with the acidic patch—conserved among remodelers. Our structures clarify mechanisms of remodeler recruitment! Link: authors.elsevier.com/a/1l2ik3vVUP...

Excited to see this out in @science.org today!! www.science.org/doi/10.1126/...

🔬 New from the Farnung Lab: We established a fully in vitro reconstituted chromatin replication system and report the first cryo-EM snapshots of the human replisome engaging nucleosomes. Brilliant work by @felixsteinruecke.bsky.social with support from @jonmarkert.bsky.social! tinyurl.com/replisome

Microsatellites are essential genomic components increasingly linked to transcriptional regulation. FoxP3, a transcription factor critical for regulatory T cell (Treg) development, recognizes TTTG repeat microsatellites by forming multimers along DNA. However, FoxP3 also binds a broader range of TnG repeats (n = 2–5), often at the edges of accessible chromatin regions. This raises questions about how FoxP3 adapts to sequence variability and the potential role of nucleosomes. Using cryoelectron microscopy and single-molecule analyses, we show that murine FoxP3 assembles into various distinct supramolecular structures, depending on DNA sequence. This structural plasticity enables FoxP3 to bridge 2–4 DNA duplexes, forming ultrastable structures that coordinate multiple genomic loci. Nucleosomes further facilitate FoxP3 assembly by inducing local DNA bending, creating a nucleus that recruits distal DNA elements through multiway bridging. Our findings thus reveal FoxP3’s unusual ability to shapeshift to accommodate evolutionarily dynamic microsatellites and its potential to reinforce chromatin boundaries and three-dimensional genomic architecture.

Ultrastable and versatile multimeric ensembles of FoxP3 on microsatellites www.cell.com/molecular-ce...
▶️FoxP3 recognizes a variety of TnG repeat microsatellites
▶️FoxP3 multimers are ultrastable, can bridge 2–4 DNA duplexes
▶️Nucleosomes can facilitate FoxP3 assembly by inducing local DNA bending

Thank you!

Very interesting finding!

8/ We propose that H3K27me3 mimicry has repeatedly emerged through evolution to restrict the spread of Polycomb domains by breaking the PRC2-H3K27me3 positive feedback loop.

7/ We find that the allosteric regulatory activities of JARID2 and PALI1 synergise to antagonise PRC2 during mouse development and restrict the spread of Polycomb domains in mECS.

6/ Unexpectedly, the H3K27me3 mimicry-defective JARID2 K116R exhibited a homeotic transformation characteristics of Polycomb gain-of-function!

This seemingly goes against the prevalent paradigm where JARID2 K116me3 is believed to positively regulate PRC2.

5/ To determine what is the function of H3K27me3 mimicry, we used CRISPR/Cas to generate 3 knock-in mouse lines: each included a single K-to-R mutation that specifically prevents JARID2, PALI1 or PALI2 from mimicking H3K27me3.

a black and white photo of a man working on a car . ALT: a black and white photo of a man working on a car .

4/ Why do JARID2 and PALI1/2 mimic H3K27me3? They are thought to "jump start" PRC2 in the absence of H3K27me3, to initiate H3K27me3 de novo. While this model agrees with biochemical and KO+rescue experiments in cells, it was never tested in vivo.

3/ H3K27me3 binds to PRC2. Some proteins mimic H3K27me3 to directly interact with the H3K27me3-binding site in PRC2.

- The Margueron lab showed it for JARID2: pmc.ncbi.nlm.nih.gov/articles/PMC...
- We showed it for PALI1/2: www.nature.com/articles/s41...

Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains The Polycomb repressive complex 2 (PRC2) is essential for normal development by maintaining developmental gene repression. PRC2 deposits the repressive chromatin mark H3 lysine 27 tri-methyl (H3K27me3...

2/ Credit first: Led by Samuel Agious, a PhD student in the @davidovichlab.bsky.social, @monashuniversity.bsky.social, through collaboration with the Eddy McGlinn lab.
www.biorxiv.org/content/10.1...

1/ H3K27me3 mimicry has repeatedly emerged through evolution, but what's the physiological relevance?

We show that JARID2 and PALI1 mimic H3K27me3 to antagonise PRC2 in vivo and restrict the spread of Polycomb domains.
🧵
www.biorxiv.org/content/10.1...