The DUBle Life of Polycomb Complexes Bernd Schuettengruber, Giacomo Cavalli  Developmental Cell  Volume 18, Issue 6, Pages 878-880 (June 2010) DOI: 10.1016/j.devcel.2010.06.001 Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 1 A New PRE-Associated Polycomb Repressive Complex Contributes to HOX Gene Silencing The Polycomb repressive complex (PR-DUB) identified by Scheuermann et al. contains histone H2A deubiquitinase activity and is associated with Polycomb response elements (PRE). All known PRE-associated PcG complexes with enzymatic activities are shown here. PRC2 contains methyltransferase activity specific for trimethylation of histone H3 lysine 27 (H3K27me3, blue lollipops), a histone mark that can induce gene silencing via recruitment of PRC1. Three speculative models are shown to explain the action of PR-DUB in chromatin silencing. (A) Left, Scheuermann et al. (2010) suggest that the balanced action of H2A ubiquitination by PRC1/dRAF and H2A deubiquitination by PR-DUB on lysine 119 (H2AK119ub1, green stars) is essential for Hox gene silencing. H2A ubiquitination and deubiquitination might have to occur at distinct locations or in a temporally regulated manner, to maintain gene repression. Right, alternatively, hyperubiquitination due to loss of PR-DUB might interfere with other repressive marks (such as H3K27me3). (B) Left, silencing might be mediated by an unknown factor (R, orange) that “reads” the H2Aub mark. Right, global hyperubiquitination of H2A induced by mutation of PR-DUB might redistribute this H2Aub reader component away from endogenous targets to ectopic sites. (C) Left, dRing activity is itself controlled by the ubiquitin system. Right, PR-DUB might deubiquitinate dRing or other PcG proteins, thereby regulating their activity or chromosomal distribution. Developmental Cell 2010 18, 878-880DOI: (10.1016/j.devcel.2010.06.001) Copyright © 2010 Elsevier Inc. Terms and Conditions