Evan Healy
@evhealy.bsky.social
Research fellow studying all things chromatin, transcription & RNA Monash University, Melbourne, Australia 🇮🇪
We are pleased to welcome 8 new fellows to our Pathway to Independence programme. Welcome Maëlle Bellec, @iamzico.bsky.social, @evhealy.bsky.social, @josepmercadal.bsky.social, @nikhil-mishra.bsky.social, Jessica Perochon, Yamini Ravichandran & Margherita Zamboni. Read more⤵️ tinyurl.com/4bk4wrk7
We are excited to be recruiting into 3 Associate Professorship's in @oxfordbiochemistry.bsky.social. Come join us as a colleague and benefit from our vibrant and multidisciplinary environment. Reach out to me if you have any questions. Please repost! (tinyurl.com/48deybuu) (tinyurl.com/4pdvjaft).
☕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
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...
bit.ly
1/ 🧵 In our new paper, we show that JARID2 and PALI1 mimic H3K27me3 to antagonise PRC2. www.cell.com/molecular-ce...
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...
cell.com
Synovial sarcoma is driven almost exclusively by a single oncofusion – SS18-SSX For years, the assumptions on disease mechanisms were simple: ➡️ SS18-SSX works by hijacking SWI/SNF chromatin remodeling activity Our new study shows that assumption was wrong 🧵👇 www.biorxiv.org/content/10.6...
SS18-SSX co-opts P300 to sustain oncogenic transcription independent of SWI/SNF activity
Synovial sarcoma is driven by the SS18-SSX fusion oncoprotein, which has been assumed to promote tumorigenesis through its incorporation into the SWI/SNF chromatin remodeling complexes. Accordingly, therapeutic efforts have focused on targeting SS18-SSX containing SWI/SNF assemblies, yet these approaches have produced limited clinical benefit. Here, we demonstrate that SS18-SSX sustains oncogenic transcription independent of SWI/SNF activity. Despite efficient degradation and dismantling of SWI/SNF complexes, fusion occupancy at target loci and associated gene expression programs remain largely intact. Instead, we identify the acetyltransferase P300 as an essential co-factor supporting SS18-SSX chromatin binding and transcriptional activation. Targeting P300 displaces the fusion from chromatin, suppresses its transcriptional output, compromising synovial sarcoma viability. Notably, dual PROTAC mediated degradation of P300 and SWI/SNF produces strong synergistic effects, broadly disrupting SS18-SSX localization and function. These findings redefine the mechanistic basis of synovial sarcoma and reveal a mechanistically anchored therapeutic strategy for targeting its core oncogenic driver. ### Competing Interest Statement C.R.V. has been a consultant for Flare Therapeutics, Roivant Sciences and C4 Therapeutics; has served on the advisory boards of KSQ Therapeutics, Syros Pharmaceuticals and Treeline Biosciences; has received research funding from Boehringer Ingelheim and Treeline Biosciences; and owns stock in Treeline Biosciences. S.A.A. has been a consultant and/or shareholder for Neomorph, Imago Biosciences, Hyku Therapeutics, C4 Therapeutics, Accent Therapeutics and Nimbus Therapeutics; and has received research support from Janssen and Syndax. N.O.C. is a co-founder, shareholder and management consultant for PhenoTherapeutics Ltd; and a shareholder in Amplia Therapeutics Ltd All other authors declare no financial interests UKRI, EP/X039633/1 Worldwide Cancer Research, https://ror.org/031tfbz57, 21-0271 Science Foundation Ireland, https://ror.org/0271asj38, 18/SIRG/5573
biorxiv.org
Very happy to see our paper published online natcomms.nature.com. Thank you to @wellcometrust.bsky.social for funding this work during my time with @robklose.bsky.social and David Booth! Thanks also to collaborators @garcialabms.bsky.social @alexdemendoza.bsky.social and the other authors!
Chromatin profiling identifies putative dual roles for H3K27me3 in regulating cell type-specific genes and transposable elements in choanoflagellates
Nature Communications - Here, the authors investigate chromatin-based gene regulation in the closest relative of animal, choanoflagellates. They uncover a putative dual role for the histone...
rdcu.be
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 🧵
Come join us in Geneva for everything epigenetics and gene regulation. It will be a great meeting! Please repost! www.keystonesymposia.org/conferences/...
Epigenetics and Gene Regulation in Health and Disease: Linking Basic Mechanisms with Therapeutic Opportunities | Keystone Symposia
Join us at the Keystone Symposia on Epigenetics and Gene Regulation in Health and Disease: Linking Basic Mechanisms with Therapeutic Opportunities, March 2026, in Geneva, with field leaders!
keystonesymposia.org
🧵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
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. ...
biorxiv.org
Many proteins bind RNA, yet we still don’t know what RNAs most bind because methods map one RBP at a time. In @cp-cell.bsky.social, with the Jovanovic lab, we describe SPIDR – a method for mapping the RNA binding sites of dozens of RBPs in a single experiment. www.sciencedirect.com/science/arti...
We are looking for new colleagues to come join us in Galway as group leaders (Junior and Senior). The Centre for Chromosome Biology is a great place and it is a good time to join. Please reach out if you want to chat about the opportunity! www.nature.com/naturecareer...
I am looking for a new postdoc to join the lab. Interested in pluripotency, germ cells, and in investigating these in a genetically tractable cnidarian? Get in touch! We offer a long-term contract, excellent research environment, and a lovely city #Galway. www.urifranklab.org
My group is hiring a new Postdoc to work on gene regulation and chromatin in Nematostella. Please RT! For more information see here: gahanlab.com tinyurl.com/34xke35d
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 👇
Eimear Lagan@eimearlagan.bsky.social · last yr.Excited to share our new paper out today in @cp-molcell.bsky.social! We show that the H3K27M oncohistone rewires cPRC1, creating a unique dependency on CBX4/PCGF4-containing complexes, and also reveal a previously unknown function of CBX4. Highlights below (1/11).
Excited to share our new paper out today in @cp-molcell.bsky.social! We show that the H3K27M oncohistone rewires cPRC1, creating a unique dependency on CBX4/PCGF4-containing complexes, and also reveal a previously unknown function of CBX4. Highlights below (1/11).
Delighted to share the latest preprint from the lab led by Janith Seneviratne We reveal novel roles for #embryonic regulators DPPA2/4 in facilitating a H2AK119Ub primed #chromatin state when aberrantly up-regulated in non-small cell lung #cancers 🧬🔬 (1/6) www.biorxiv.org/content/10.1...
👋 Meet our new Scientific Head - Professor Jose Polo! A world leader in epigenetics & stem cell biology, Prof Polo (SAiGENCI, University of Adelaide, Monash University) brings his deep expertise & passion for advancing life sciences in Aus & beyond. 🌏 We're thrilled to have him on board! 👏
Prof Jose Polo appointed as EMBL Australia Scientific Head | EMBL Australia
Professor Jose Polo has been appointed as the new Scientific Head of EMBL Australia. A globally recognised leader in epigenetics and stem cell biology, Prof Polo brings extensive expertise and a passi...
emblaustralia.org
📣 A reminder about an open postdoctoral position in our group! 🧫 Are you interested in mechanisms of gene regulation, human facial development and disease? How our DNA shapes the way we look? Do you love chromatin and enhancers? 🧬 If so, reach out for an informal chat! 💬 longlab.co.uk
Postdoctoral Researcher
Our research is focused on understanding how genetic changes in the non-coding genome can impact gene regulatory mechanisms, alter developmental processes and ultimately affect human craniofacial shap...
elxw.fa.em3.oraclecloud.com
The Americans are doing to Kseniia what the Russians did to Brittney Griner for having 0.7 grams of cannabis oil. Except no one is coming to negotiate her freedom and Harvard is sitting on their hands. I am so ashamed. Please share this story. www.nytimes.com/2025/04/11/s...
She Worked in a Harvard Lab to Reverse Aging, Until ICE Jailed Her (Gift Article)
President Trump’s immigration crackdown ensnared Kseniia Petrova, a scientist who fled Russia after protesting its invasion of Ukraine. She fears arrest if she is deported there.
nytimes.com
Excited to share our preprint on the molecular architecture of heterochromatin in human cells 🧬🔬w/ @jpkreysing.bsky.social, @johannesbetz.bsky.social, @marinalusic.bsky.social, Turoňová lab, @hummerlab.bsky.social @becklab.bsky.social @mpibp.bsky.social 🔗 Preprint here tinyurl.com/3a74uanv
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...
Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains https://www.biorxiv.org/content/10.1101/2025.03.13.642955v1
We used cryoET and biophysical approaches in vitro together with molecular biology in differentiated cells to show that chromatin compacted by PRC1-CBX8 is porous and accessible while PRC1 is dynamic in it. 🧪🧬 #cryoET #Epigenetics #Polycomb www.nature.com/articles/s41...
Dynamic PRC1–CBX8 stabilizes a porous structure of chromatin condensates - Nature Structural & Molecular Biology
Here the authors show that a gene-inactivating protein complex packs inactive genes into a dynamic and accessible structure. The study challenges the traditional views that restricted accessibility an...
nature.com
Please see 🧵by @evhealy.bsky.social about our new paper exploring the role of PRC1 and PRC2 in non-dividing cells 👇
Evan Healy@evhealy.bsky.social · 2y ago🧵 1/ We’re excited to share that our new paper with @adrianbracken.bsky.social lab is out 🎉 In this study (which began over 10 years ago!), we explore the biology of PRC2 and PRC1 in non-dividing cells. We also explore the effects of PRC2 inhibitor drugs on these cells. Here’s what we found👇
🧵 1/ We’re excited to share that our new paper with @adrianbracken.bsky.social lab is out 🎉 In this study (which began over 10 years ago!), we explore the biology of PRC2 and PRC1 in non-dividing cells. We also explore the effects of PRC2 inhibitor drugs on these cells. Here’s what we found👇
Work led by graduate student @trinitycookis.bsky.social and coauthors Alexandria Lydecker, @paulsauer.bsky.social, and @kasinath-lab.bsky.social is out today where we looked at the inhibition of PRC2 by histone PTMs associated with regions of active transcription. www.nature.com/articles/s41...
Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications - Nature Structural & Molecular Biology
Structures reveal that histone H3K36me3 and H3K4me3 modifications reduce Polycomb repressive complex 2 (PRC2) function through the inhibition of histone tail engagement and antagonistic binding to the...
nature.com
"Everything in epigenetics is circular". Here, we explore how memory that is stored locally on chromatin has a crucial role in stabilising cellular state, updating our view of the epigenetic landscape from one shaped by the genotype, to one moulded by experience doi.org/10.1186/s130...
Chromatin-based memory as a self-stabilizing influence on cell identity - Genome Biology
Cell types are traditionally thought to be specified and stabilized by gene regulatory networks. Here, we explore how chromatin memory contributes to the specification and stabilization of cell states...
doi.org
AEpiA 2024 ORAL PRESENTATION PRIZE WINNERS 1st - Mark Ezegboyu (University of Otago) 2nd - @evhealy.bsky.social (Monash University) Runners up - Braydon Meyer (@garvaninstitute.bsky.social), Kate O'Hara (@csiro.bsky.social) and @scientistkate.bsky.social (@cmri.bsky.social)
A preview on the latest work from @robklose.bsky.social lab where Aleks (Not made the bluesky transition yet) used single molecule approaches to address how Polycomb controls transcription. He found that Polycomb limits the frequency with which a promoter can enter a permissive transcribing state.
nature.com
Evan Healy@evhealy.bsky.social · 2y agoHow does PRC1 counteract transcription? See this preview from @adrianbracken.bsky.social and I on an exciting new study from @robklose.bsky.social lab where they show ncPRC1 blocks the early stages of transcription. www.sciencedirect.com/science/arti... @conwayer1.bsky.social for title inspo!