🧵 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👇 - ThreadSky

evhealy.bsky.social • 40 days 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👇

Comments

danevass.bsky.social•39 days ago

Excellent work mate! Great to see it out.

evhealy.bsky.social•39 days ago

Thanks Dane!

evhealy.bsky.social•40 days ago

2/ We discovered that non-dividing cells are refractory to PRC2 inhibitors, meaning H3K27me2/3 are not reduced and gene expression is unchanged. This indicates that replicative dilution, not active H3K27 demethylation, is the main mechanism for H3K27me2/3 reduction upon inhibition of PRC2🔬

evhealy.bsky.social•40 days ago

3/ Our data shows that in quiescent cells (non-dividing), there’s a shift to less enzymatically active PRC1 (the canonical CBX containing forms) and PRC2 (containing EZH1). These changes appear to be evolutionarily conserved. 🧬

evhealy.bsky.social•40 days ago

4/ We propose that the non-enzymatic functions of EZH1-PRC2 and canonical PRC1 complexes play a critical role in maintaining long-term repression of Polycomb target genes in non-dividing cells.

evhealy.bsky.social•40 days ago

5/ Why is this important? It suggests that PRC2 inhibitors might not be effective in cancers containing non-dividing cells. ⚠️

greenrat.bsky.social•39 days ago

great work, would be reading the paper carefully.
Question - if non-enzymatic function is important - what about PROTACs against the complex?

evhealy.bsky.social•40 days ago

6/ We hope these insights will guide future cancer treatment strategies, especially in understanding how drugs interact with dividing vs. non-dividing cells. 💡

evhealy.bsky.social•40 days ago

7/ Thanks for reading! We’re excited to continue exploring these mechanisms in future work. Check out the full paper in @cp-cellreports.bsky.social for more details ! 📖

https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01543-2

nireynon.bsky.social•39 days ago

Congratulations Evan!

evhealy.bsky.social•39 days ago

Thanks Nir!

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