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Title: The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
Authors: Bracken, Adrian P
Kleine-Kohlbrecher, Daniela
Dietrich, Nikolaj
Pasini, Diego
Gargiulo, Gaetano
Beekman, Chantal
Theilgaard-Monch, Kim
Minucci, Saverio
Porse, Bo T
Marine, Chris
Hansen, Klaus H
Helin, Kristian # ×
Issue Date: Mar-2007
Publisher: Cold Spring Harbor Laboratory Press
Series Title: Genes & Development vol:21 issue:5 pages:525-530
Abstract: The p16(INK4A) and p14(ARF) 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.
URI: 
ISSN: 0890-9369
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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