New epigenetic pathway for stemness maintenance mediated by the histone methyltransferase Ezh1

The self-renewal capacity of stem cells is crucial for the homeostatic maintenance of adult tissues, in which they mediate the continuous replacement of differentiated cells, and is the focus of attempts to design patient-specific therapies. The Polycomb group proteins are key global epigenetic regulators of stem-cell fate decisions. The Polycomb family induces histone-specific posttranslational modifications on target genes through the action of the two Polycomb repressive complexes (PRC1 and PRC2). PRC2 catalyzes methylation of Lys27 on histone 3 (H3), generating the H3K27me2/3 mark, which acts as a platform for PRC1, which, in turn, ubiquitylates histone H2A on Lys119. The catalytic subunits of the PRC1 and PRC2 complexes are, respectively, Ring1B and Ezh1/2, but it should be noted that the repressive activity of the Polycomb group also requires the presence of other functional subunits. The chromatin-modifying component of PRC2 exists in two forms, Ezh1 and Ezh2, which have an identical catalytic SET domain. Therefore the exclusive attribution of methyltransferase activity to Ezh2 needs to be retested; indeed, accumulated evidence support the hypothesis that the repressive activities of PRC2Ezh1 and PRC2-Ezh2 are differentially coordinated during tissue development and homeostasis. The H3K27me3 mark is not completely lost in Ezh2 ESCs, suggesting residual or compensatory methylation by Ezh1. Moreover, Ezh1 is indispensable for the establishment of pluripontent cells and for the maintenance of ESC self-renewal. Further evidence for a role for Ezh1 comes from the New epigenetic pathway for stemness maintenance mediated by the histone methyltransferase Ezh1