EZH2 (PRC2) trimethylates H3K27 → PRC1 recruitment → chromatin compaction → transcriptional silencing.
Elegant at the mechanistic level. Consequential at the organismal level — elevated EZH2 activity shortens lifespan in model organisms, likely via progressive silencing of stress-response loci.
The SET domain may be one of the most underrated targets in aging biology.
#EZH2 #PRC2 #Epigenetics #AgingBiology #H3K27me3 #ChromatinRemodeling #Longevity
The intricate mechanisms of #epigenetic silencing.
#PRC2 #Arabidopsis #VIN3 #VRN5
https://phys.org/news/2023-10-intricate-mechanisms-epigenetic-silencing.html
Epigenetic silencing, which involves the suppression of gene activity, is a fascinating and increasingly influential branch of biological sciences. It allows cells to remember and maintain specific gene expression patterns throughout development and respond to environmental cues such as winter cold in the case of vernalization in plants.
Development of a potent EED-targeted #PRC2 degrader, UNC7700, highly effective after 24 h in a diffuse large B-cell lymphoma DB cell line:
PROTAC Linkerology Leads to an Optimized Bivalent Chemical Degrader of Polycomb Repressive Complex 2 (PRC2) Components https://pubs.acs.org/doi/10.1021/acschembio.2c00804
Alice Frolov
CellBioNews
CavalliLab
The EMBO Journal