2. Academic Validation
  3. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells

The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells

  • Genes Dev. 2007 Mar 1;21(5):525-30. doi: 10.1101/gad.415507.
Adrian P Bracken 1,  Daniela Kleine-Kohlbrecher,  Nikolaj Dietrich,  Diego Pasini,  Gaetano Gargiulo,  Chantal Beekman,  Kim Theilgaard-Mönch,  Saverio Minucci,  Bo T Porse,  Jean-Christophe Marine,  Klaus H Hansen,  Kristian Helin
Affiliations

Affiliation

  • 1 Centre for Epigenetics, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen 2200, Denmark. [email protected]
PMID: 17344414 DOI: 10.1101/gad.415507
Abstract

The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet the mechanisms triggering their up-regulation are not well understood. Here, we show that the ability of the oncogene BMI1 to repress the INK4A-ARF locus requires its direct association and is dependent on the continued presence of the EZH2-containing Polycomb-Repressive Complex 2 (PRC2) complex. Significantly, EZH2 is down-regulated in stressed and senescing populations of cells, coinciding with decreased levels of associated H3K27me3, displacement of BMI1, and activation of transcription. These results provide a model for how the INK4A-ARF locus is activated and how Polycombs contribute to Cancer.

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