Figure 5. Deregulation of PcG Activity in Cancer.

(A) Proposed model for PcG gene dosage and its effect on stem cells and cancer development. Briefly, adequate PcG gene expression levels seem to be essential to maintain homeostasis and normal stem cell function. Gain or loss of PcG functions, such as deregulated expression or mutations, lead to increased tumor development, possibly by modifying the composition or perturbing the stoichiometry of the complexes. In turn, complete ablation of PcG activity appears to be detrimental and leads to impaired self-renewal and loss of stem cells.

(B) Schematic representation of the balance between PcG-mediated H3K27me3 and MLL complex-mediated H3K4me3 modifications in the maintenance of a transcriptional program. The function of many proteins from these complexes is altered by aberrant expression (yellow star), by missense mutations (blue star), or by chromosomal translocations (red star) in human cancers (Agger et al., 2009; Dalgliesh et al., 2010; Krivtsov and Armstrong, 2007; van Haaften et al., 2009; Wang et al., 2009; Xiang et al., 2007), likely leading to changes in transcriptional programs and cell states.

(C) Expression of Ezh2 and Bmi1 is regulated at the post-transcriptional level by miRNAs, targeting their 3′UTR, leading to transcript degradation.

(D) Multiple chimeric proteins resulting from chromosomal translocations found in human cancers interact with PRC1 and PRC2 complexes and appear to recruit them to target genes. AF9. ENL and TEL are found in multiple chromosomal translocation-derived fusion proteins in human cancers. The asterisk indicates that, although actual recruitment of PRC1 by the fusion proteins remains to be proven, the AF9, ENL, and TEL domains interacting with PRC1 proteins are present in the fusion proteins and are essential for their oncogenic activity (Boccuni et al., 2003; García-Cuéllar et al., 2001; Hemenway et al., 2001).