Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor.

An important facet of transcriptional repression by Polycomb repressive complex 1 (PRC1) is the mono-ubiquitination of histone H2A by the combined action of the Posterior sex combs (Psc) and Sex combs extra (Sce) proteins. Here, we report that two ubiquitin-specific proteases, USP7 and USP11, co-purify with human PRC1-type complexes through direct interactions with the Psc orthologues MEL18 and BMI1, and with other PRC1 components. Ablation of either USP7 or USP11 in primary human fibroblasts results in de-repression of the INK4a tumour suppressor accompanied by loss of PRC1 binding at the locus and a senescence-like proliferative arrest.

Role for the MOV10 RNA helicase in polycomb-mediated repression of the INK4a tumor suppressor.

Several lines of evidence point to a role for noncoding RNA in transcriptional repression by Polycomb group (PcG) proteins, but the precise mechanism remains unclear. Here we show that human MOV10, a putative RNA helicase previously implicated in post-transcriptional gene silencing, co-purifies and interacts with components of Polycomb-repressive complex 1 (PRC1) from human cells. Endogenous human MOV10 is mostly nuclear, and a proportion associates with chromatin in an RNA-dependent manner.

Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.

Misexpression of Polycomb repressive complex 1 (PRC1) components in human cells profoundly influences the onset of cellular senescence by modulating transcription of the INK4a tumor suppressor gene. Using tandem affinity purification, we find that CBX7 and CBX8, two Polycomb (Pc) homologs that repress INK4a, both participate in PRC1-like complexes with at least two Posterior sex combs (Psc) proteins, MEL18 and BMI1. Each complex contains a single representative of the Pc and Psc families.