Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

Item Type:Article
Title:The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
Creators Name:Bracken, A.P. and Kleine-Kohlbrecher, D. and Dietrich, N. and Pasini, D. and Gargiulo, G. and Beekman, C. and Theilgaard-Moench, K. and Minucci, S. and Porse, B.T. and Marine, J.-C. and Hansen, K.H. and Helin, K.
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.
Keywords:Senescence, Cancer, INK4B, INK4A, ARF, Polycomb, Animals, Mice
Source:Genes & Development
ISSN:0890-9369
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Volume:21
Number:5
Page Range:525-530
Date:1 March 2007
Official Publication:https://doi.org/10.1101/gad.415507
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library