The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells.
Research output: Contribution to journal › Journal article › Research › peer-review
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.
| Original language | English |
|---|---|
| Journal | Genes & Development |
| Volume | 21 |
| Issue number | 5 |
| Pages (from-to) | 525-30 |
| Number of pages | 5 |
| ISSN | 0890-9369 |
| DOIs | |
| Publication status | Published - 2007 |
Bibliographical 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
ID: 5034677