Pierre Romero, Laia Richart, Setareh Aflaki, Ambre Petitalot, Megan Burton, Audrey Michaud, Julien Masliah-Planchon, Frédérique Kuhnowski, Samuel Le Cam, Carlos Baliñas-Gavira, Céline Méaudre, Armelle Luscan, Abderaouf Hamza, Patricia Legoix, Anne Vincent-Salomon, Michel Wassef, Daniel Holoch, Raphaël Margueron
Mutations in chromatin regulators are widespread in cancer. Among them, the histone H3 lysine 27 methyltransferase Polycomb Repressive Complex 2 (PRC2) shows distinct alterations according to tumor type. This specificity is poorly understood. Here, we model several PRC2 alterations in one isogenic system to reveal their comparative effects. Focusing then on lymphoma-associated EZH2 mutations, we show that Ezh2Y641F induces aberrant H3K27 methylation patterns even without wild-type Ezh2, which are alleviated by partial PRC2 inhibition...
April 24, 2024: Nature Communications