多梳蛋白家族蛋白结合于整个INK4A-ARF基因座，并在衰老细胞中解离。
The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells.
作者信息
Bracken Adrian P, Kleine-Kohlbrecher Daniela, Dietrich Nikolaj, Pasini Diego, Gargiulo Gaetano, Beekman Chantal, Theilgaard-Mönch Kim, Minucci Saverio, Porse Bo T, Marine Jean-Christophe, Hansen Klaus H, Helin Kristian
机构信息
Centre for Epigenetics, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen 2200, Denmark.
出版信息
Genes Dev. 2007 Mar 1;21(5):525-30. doi: 10.1101/gad.415507.
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.
摘要
由INK4A-ARF基因座编码的p16INK4A和p14ARF蛋白是细胞衰老的关键调节因子，但其上调的触发机制尚不清楚。在这里，我们表明致癌基因BMI1抑制INK4A-ARF基因座的能力需要其直接结合，并且依赖于含EZH2的多梳抑制复合物2（PRC2）的持续存在。值得注意的是，EZH2在应激和衰老细胞群体中下调，这与相关的H3K27me3水平降低、BMI1的移位和转录激活相吻合。这些结果为INK4A-ARF基因座如何被激活以及多梳蛋白如何促进癌症提供了一个模型。
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