@article{5b764bb0531911dd8d9f000ea68e967b,
title = "The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells.",
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.",
author = "Bracken, {Adrian P} and Daniela Kleine-Kohlbrecher and Nikolaj Dietrich and Diego Pasini and Gaetano Gargiulo and Chantal Beekman and Kim Theilgaard-M{\"o}nch and Saverio Minucci and Porse, {Bo T} and Jean-Christophe Marine and Hansen, {Klaus H} and Kristian Helin",
note = "Keywords: Animals; Cell Aging; Cell Line; Chromatin Immunoprecipitation; Cyclin-Dependent Kinase Inhibitor p16; DNA-Binding Proteins; Down-Regulation; Embryo, Mammalian; Fibroblasts; Genes, p16; Histones; Humans; Methylation; Mice; Mice, Inbred C57BL; Neoplasms; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Proteins; Proto-Oncogene Proteins; Repressor Proteins; Stem Cells; Transcription Factors; Tumor Suppressor Protein p14ARF",
year = "2007",
doi = "10.1101/gad.415507",
language = "English",
volume = "21",
pages = "525--30",
journal = "Genes & Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "5",
}
