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

Adrian P. Bracken, 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)525-530
Number of pages6
JournalGenes and Development
Volume21
Issue number5
DOIs
Publication statusPublished - Mar 1 2007

Keywords

  • ARF
  • Cancer
  • INK4A
  • INK4B
  • Polycomb
  • Senescence

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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