JMJD3 as a Pivotal Factor in NOTCH1-Mediated Oncogenic Activation in T-cell Leukemia. A) Schematic representation of the H3K27me3 writer (the polycomb complex, left) and eraser (JMJD3, right). EZH2 contains the catalytic subunit of the complex through its SET domain, whereas the EED subunit recognizes the H3K27me3 mark and aids in polycomb binding. JmjC domain activity is inhibited by the small molecule inhibitor GSKJ4. B) The main idea about the key role of JMJD3 in the NOTCH1transcriptional complex. Before activation of the NOTCH1 signaling pathway, the promoters of classical NOTCH1 target genes are bound by RBP-Jk, together with components of the co-repressor complexes and PRC2, leading to low gene expression. After the binding of NOTCH1 and its co-activator MAML1, the genes are activated through the recruitment of JMJD3 and the MLL complex, with simultaneous eviction of PRC2, which leads to the demethylation of H3K27me3 and the methylation of H3K4me3.Reprinted by permission from Macmillan Publishers Ltd: Nature. Volume 514: pg. 513-517, copyright 2014.