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
Volume:	21
Number:	5
Page Range:	525-530
Date:	1 March 2007
Additional Information:	Erratum in: Genes Dev 37(17-18):861
Official Publication:	https://doi.org/10.1101/gad.415507
PubMed:	View item in PubMed

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