(A) In a proliferating progenitor cell, the activation of differentiation related genes results in cessation of proliferation.
(B) The loss of SMARCB1 in RT cells results in the replacement of SWI/SNF complexes with Polycomb silencing complexes at differentiation driving genes, thus preventing differentiation.
(C) Treatment of RT cells with EZH2 inhibitors leads to removal of H3K27me3 modifications and results in NSD1 writing H3K36me2 activating modifications in its place, activating differentiation associated genes and causing cell arrest/death.
(D) The loss of NSD1 impairs the gain of H3K26me2 and blocks the cell death otherwise caused by EZH2 inhibition.
Figure created with BioRender.com