Chen Davidovich

Figure 1.(A) Classical gel electrophoresis experiments showing mono-, di-, tri-, tetra-, and further multinucleosome bands upon chromatin digestion. (B) The nucleosome repeat length (NRL) is defined as the genomic distance between the centres of two neighbouring nucleosomes.

Figure 2.Nucleosome mapping using MNase-seq versus ATAC-seq. (A) In MNase-seq, nucleosomes in both open and tightly packed genomic regions are accessible to digestion. MNase preferentially cleaves DNA between nucleosomes and digests DNA until it encounters a histone octamer, which provides a footprint of nucleosome-protected DNA regions. (B) Bulk MNase-seq results in averaged maps across millions of cells, effectively capturing all possible nucleosome positioning configurations. (C) Single-cell MNase-seq (scMNase-seq) results in a noisier and sparser signal. The resulting footprints still represent nucleosome-protected regions, but not all nucleosomes are represented. (D) In ATAC-seq, open regions can be accessed by the enzyme Tn5 transposase, which can insert primers in regions free from the binding of nucleosomes and transcription factors (TFs). (E) For open chromatin regions, nucleosome maps can be obtained from ATAC-seq similar to MNase-seq. (F) Closed, tightly packed chromatin regions may be less represented in ATAC-seq nucleosome maps.

Figure 5.Molecular mechanisms affecting nucleosome spacing. (A) Linker histones H1 and nonhistone chromatin proteins which compete with H1s and modulate nucleosome spacing through structural and electrostatic mechanisms. (B) Chromatin remodellers actively reposition nucleosomes following context-dependent rules. (C) Cell state-dependent chromatin boundaries formed by CTCF and other structural proteins, as well as associated recruitment of chromatin remodellers which space nucleosomes. (D) Gene activity associated with remodeller action and RNA polymerases transcribing through the nucleosomes, leading to smaller distances between nucleosomes in regulatory regions and gene bodies. (E) DNA sequence repeats of different types.

Figure 6. Examples of NRL changes in biological systems. (A) Cell differentiation leads to NRL changes between different cell types, e.g. mouse dorsal root ganglia neurons (NRL ∼165 bp) versus cortical astrocytes (NRL ∼183 bp) [175]. Schematic cell shapes are adapted from an image created in BioRender (https://BioRender.com/89trj2t). (B) Paired normal versus tumour breast tissues show NRL shortening in cancer (figure adapted from [36] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)). (C) Nucleosome positioning derived from cfDNA of human volunteers shows NRL increase with age (figure reprinted from [79] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)).

Nucleosome aficionados! Our new review "Nucleosome spacing across cell types, diseases, and ages" is out in NAR: academic.oup.com/nar/article/...

A huge effort to pull together what we’ve learned about nucleosome spacing in many systems. Enjoy!
@milena-bikova.bsky.social @chrsclrksn.bsky.social

Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains Some proteins mimic the repressive mark H3K27me3, but the physiological relevance of this phenomenon was unclear. Agius et al. show that the PRC2 subunits JARID2 and PALI1 mimic H3K27me3 to antagonize PRC2-mediated H3K27me3 deposition, limit Polycomb domain spreading, and enable timely activation of developmental genes in vivo.

Online Now: Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains Online now:

5/ A fantastic collaboration between the @davidovichlab.bsky.social and @eddymcglinn.bsky.social labs, led by a brilliant PhD student, @samagius.bsky.social, who is now looking for a postdoc position!

4/ We propose that H3K27me3 mimicry has repeatedly emerged during evolution as a mechanism to antagonise PRC2 and restrict the spread of Polycomb domains.

3/ In mouse ESCs, the same mutations lead to increased H3K27me3 levels and enhanced spreading of Polycomb domains.

3/ In mice, we show that mutations that disrupt H3K27me3 mimicry delay the activation of Hox genes and cause homeotic transformations characteristic of Polycomb gain of function.

2/ Some accessory subunits of PRC2 mimic the repressive mark H3K27me3. Although this mechanism was proposed to “jump-start” PRC2 during de novo H3K27me3 deposition, its physiological relevance remained unknown.

Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains Some proteins mimic the repressive mark H3K27me3, but the physiological relevance of this phenomenon was unclear. Agius et al. show that the PRC2 subunits JARID2 and PALI1 mimic H3K27me3 to antagonize...

1/ 🧵 In our new paper, we show that JARID2 and PALI1 mimic H3K27me3 to antagonise PRC2. www.cell.com/molecular-ce...

DOT1L provides transcriptional memory through PRC1.1 antagonism - Nature Cell Biology Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibit...

☕Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.
bit.ly/46MZ3Di

1/3 New bioRxiv preprint from the lab: “Minute-scale coupling of chromatin marks and transcriptional bursts”. Led by Xiohui Gao & Chaebeen Ko. bioRxiv : www.biorxiv.org/cgi/content/...

Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3 https://www.biorxiv.org/content/10.64898/2026.02.05.704038v1

Epigenetics Update - DOT1L provides transcriptional memory through PRC1.1 antagonism go.nature.com/4qh5aXB

Chen Davidovich and Omer Gilan (Monash University) reporting in Nat Cell Biol

#Epigenetics #DOT1L #PolyComb
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Gain deeper insights into gene regulation; epigenometech.com

Unbalanced chromatin binding of Polycomb complexes drives neurodevelopmental disorders Borges, González-Blanco, Arigela, et al. report new missense mutations in the PRC1 genes RNF2 and RING1 in individuals with neurodevelopmental disorders. Functional dissection of a deleterious variant...

Very excited to share our new Molecular Cell paper on missense mutations in Polycomb genes and how they can disrupt chromatin regulation to drive neurodevelopmental disorders. A huge thank you to everyone involved, and to our amazing collaborators!
www.cell.com/molecular-ce...

DOT1L provides transcriptional memory through PRC1.1 antagonism - Nature Cell Biology Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibit...

H3K79me2/3 is sufficient to antagonise PRC1 www.nature.com/articles/s41...

DOT1L provides transcriptional memory through PRC1.1 antagonism - Nature Cell Biology Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibit...

www.nature.com/articles/s41...

happy i could be a part of this paper from the Gilan lab out now. Along with many other things, it provides strong evidence of chromatin memory for gene activation, and suggests that DOT1L is the missing link balancing the fast and slow arms of the MLL/Polycomb axis

Science update from my postdoc Peiyuan Chai - his work “glycoRNA complexed with heparan sulfate regulates VEGF-A signaling” is now published @nature.com uncovering a new layer or glycoRNA-regulation of growth factor mediated control physiological processes rdcu.be/e1bBX

Tom Cech to Davos: RNA research is 'still a big deal' The Nobel laureate and CU Boulder professor, recently ranked #1 globally for RNA research, will speak at the World Economic Forum annual meeting in Davos,

www.colorado.edu/today/2026/0...

Dynamic evolution of EZHIP, an inhibitor of the Polycomb Repressive Complex 2 in mammals The Polycomb Repressive Complex 2 (PRC2) is an ancient, conserved chromatin-interacting complex that controls gene expression, facilitating differentiation and cellular identity during development. It...

@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/

Two alternative isoforms of PRC2 accessory subunit AEBP2 modulate developmental Polycomb functions in opposite ways - with broadly-expressed AEBP2L acting as an intrinsic inhibitor in somatic cells
@adrianbracken.bsky.social @davidovichlab.bsky.social and colleagues
www.embopress.org/doi/full/10....

KSQA: Dr Karim-Jean Armache / Dr. Cigall Kadoch (Epigenetics and Gene Regulation) YouTube video by KeystoneSymposia

@ckadoch.bsky.social and I are excited to welcome you to Geneva for the 2026 Keystone Symposium on Epigenetics and Gene Regulation in Health and Disease — short talk and poster slots are still open. Don’t miss the deadlines.
Video: youtu.be/sLfyuQuH8F0

2/ Done in collaboration with the lab of @adrianbracken.bsky.social, who wrote a great 🧵 explaining the work. bsky.app/profile/adri...

Auto-inhibition of PRC2 by the broadly expressed long isoform of AEBP2 | The EMBO Journal imageimageAEBP2 is an accessory subunit of the PRC2 complex previously implicated both in promoting and antagonizing Polycomb repressive activity. This study reveals that its alternative isoforms, AEB...

1/ It's long been assumed that AEBP2 recruit PRC2 to chromatin. Now, we show that AEBP2 usually does the exact opposite:
The only isoform of AEBP2 that is expressed in most cell types and tissues inhibits the chromatin-binding activity of PRC2. www.embopress.org/doi/full/10....

1/ 🚀 AEBP2 isn’t what we thought.

You were told that AEBP2 promotes PRC2 activity on chromatin.

We found the opposite: the most prevalent AEBP2 isoform inhibits PRC2 activity.

👉 surl.li/cgwqcq

A thread 🧵

Abstract extension flyer. Deadline extended to Friday 31st October

📣 Abstract Deadline Extended!
Due to popular demand, we’ve extended the submission deadline — giving you a few extra days to finalise your abstract.
Don’t miss out on being part of Lorne’s legacy!
👉 Submit today: www.lorneproteins.org
#LorneProteins #DeadlineExtended #ProteinScience

Screenshot of tweet from the ARC saying they will announce DP26 outcomes on Tuesday 28th Oct, and LP25r1 outcomes on Wednesday 29th.

ARC says Discovery Projects outcomes will be tomorrow (Tuesday). Linkage Projects (2025, round 1) on Wed. Over past ~year, it's often been at about 11am (Canberra).

My bot will pick up the change to RMS & post immediately.

ARC should email outcomes to lead CIs, but might take an 1hr or so for DPs

AEBP2-Directed H3K27me2 Defines a Specific Vulnerability in EZH2-mutant Lymphoma The catalytic subunit of Polycomb Repressive Complex 2 (PRC2), EZH2, is recurrently mutated in 25% of diffuse large B-cell lymphomas (DLBCL), causing increased H3K27me3 and decreased H3K27me2 levels. ...

🧵1/Exciting news in cancer epigenetics! Our latest research, "AEBP2-Directed H3K27me2 Defines a Specific Vulnerability in EZH2-mutant Lymphoma", is now available on www.biorxiv.org/content/10.1.... Here's a thread summarizing our findings!👇
#CancerResearch #Epigenetics #Chromatin #Lymphoma

EEE meeting is BACK! Early Embryogenesis & Epigenetics conference in Berlin 02/2026.
Checkout great program and over 12 slots for (not so) short talks for submitted abstracts!. Early registration now open -
w.molgen.mpg.de/embryo2026

Rewiring of chromatin regulation underlies the evolution of brown algal multicellularity Chromatin structure plays a central role in regulating transcription, genome stability, and epigenetic inheritance in eukaryotes. Much of our understanding of chromatin architecture and histone post-t...

Super glad to contribute to this study on chromatin evolution in brown algae! Special thanks to Jeromine Vigneau, @borglab.bsky.social and Susana Coelho for making this happen.

www.biorxiv.org/content/10.1...

Genes and Gin: A Synthetic Biology Social 🎉

Join us for a fun night of Genes and Gin - learn to play the synthetic card game "Remediate!", created by a group of researchers within our Centre.

Make sure you register for catering:
www.eventbrite.com.au/e/genes-and-...

See you on the rooftop!

Many of the most complex and useful functions in biology emerge at the scale of whole genomes.

Today, we share our preprint “Generative design of novel bacteriophages with genome language models”, where we validate the first, functional AI-generated genomes 🧵