H3K27M in Gliomas Causes a One-Step Decrease in H3K27 Methylation and Reduced Spreading within the Constraints of H3K36 Methylation
Ashot S. Harutyunyan, Haifeng Chen, Tianyuan Lu, Cynthia Horth, Hamid Nikbakht, Brian Krug, Caterina Russo, Eric Bareke, Dylan M. Marchione, Mariel Coradin, Benjamin A. Garcia, Nada Jabado, Jacek Majewski
Abstract
cell lines to investigate H3K27 methylation and its interaction with H3K36 and H3K9 modifications. We describe a "step down" effect of H3K27M on the distribution of H3K27 methylation: me3 is reduced to me2, me2 is reduced to me1, whereas H3K36me2/3 delineates the boundaries for the spread of H3K27me marks. We also observe a replacement of H3K27me2/3 silencing by H3K9me3. Using a computational simulation, we explain our observations by reduced effectiveness of PRC2 and constraints imposed on the deposition of H3K27me by antagonistic H3K36 modifications. Our work further elucidates the effects of H3K27M in gliomas as well as the general principles of deposition in H3K27 methylation.