E(z) Inhibitors

E(z) inhibitors are a class of small molecules that have garnered considerable attention in the field of epigenetics. E(z) stands for Enhancer of zeste, which refers to the Drosophila melanogaster gene that was originally identified as a crucial regulator of segmentation during embryonic development. The human homolog of E(z) is known as EZH2 (Enhancer of zeste homolog 2). E(z) inhibitors are specifically designed to target the catalytic SET domain of the E(z)/EZH2 protein. The SET domain is responsible for the methyltransferase activity of the protein, which catalyzes the addition of methyl groups to lysine 27 of histone H3 (H3K27). This methylation is a central epigenetic modification involved in gene regulation, and aberrant EZH2 activity has been linked to various diseases, including cancer.By binding to the SET domain of E(z)/EZH2, these inhibitors disrupt its methyltransferase activity and alter the methylation status of H3K27. Consequently, this can lead to changes in chromatin structure, affecting gene expression patterns. In some cases, E(z) inhibitors have been observed to induce gene activation, while in others, they may lead to gene repression, depending on the context and specific cellular conditions. The development and study of E(z) inhibitors have provided valuable insights into the intricacies of epigenetic regulation. Researchers use these inhibitors to dissect the roles of E(z)/EZH2 and the PRC2 complex in various cellular processes, such as development, differentiation, and cellular identity maintenance.