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Proposed model of the epigenetic regulation of the expression of genes for p16Ink4a and p19Arf by JDP2. Exposure of young primary cultures of cells to aging stress leads to the accumulation of JDP2. JDP2 binds to histones and inhibits methylation of H3K27 at the p16Ink4a/p19Arf locus. As a result, PRC-1 and PRC-2 fail to form stable repressive complexes and are released from the locus. The consequent expression of p16Ink4a and p19Arf in the aged cells leads to senescence.
