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The Polycomb group proteins bind throughout the <i>INK4A-ARF</i> 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 Porse, Jean‐Christophe Marine, Klaus Hansen, Kristian Helin

Genes & Development · 2007 · ▲ 843 citations

Cellular senescence
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Abstract

The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence(definition), 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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Provenance

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OpenAlex
DOI
10.1101/gad.415507
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2026-07-30 MST

Cite this

APA
Bracken, A.P., Kleine‐Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., Theilgaard‐Mönch, K., Minucci, S., Porse, B., Marine, J., Hansen, K., &amp; Helin, K. (2007). The Polycomb group proteins bind throughout the <i>INK4A-ARF</i> locus and are disassociated in senescent cells. <em>Genes & Development</em>. https://doi.org/10.1101/gad.415507
Vancouver
Bracken AP, Kleine‐Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, et al. The Polycomb group proteins bind throughout the <i>INK4A-ARF</i> locus and are disassociated in senescent cells. Genes & Development. 2007. doi:10.1101/gad.415507.
BibTeX
@unpublished{adrian2007ThePol, title = {The Polycomb group proteins bind throughout the <i>INK4A-ARF</i> locus and are disassociated in senescent cells}, author = {Adrian P. Bracken and Daniela Kleine‐Kohlbrecher and Nikolaj Dietrich and Diego Pasini and Gaetano Gargiulo and Chantal Beekman and Kim Theilgaard‐Mönch and Saverio Minucci and Bo Porse and Jean‐Christophe Marine and Klaus Hansen and Kristian Helin}, journal = {Genes & Development}, year = {2007}, doi = {10.1101/gad.415507}, }

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