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. Author manuscript; available in PMC: 2015 Jul 1.
Published in final edited form as: Trends Mol Med. 2014 May 28;20(7):375–384. doi: 10.1016/j.molmed.2014.04.004

Figure 2. Schematic showing regulation of the INK4a/ARF (CDKN2a) locus.

Figure 2

Repression of the locus in healthy, self-renewing cells is mediated by the histone-modifying activities of the PRC1 (protein regulator of cytokinesis 1, orange) and PRC2 (protein regulator of cytokinesis 1, green) Polycomb Group complexes. The PRC1 complex contains BMI1 (B Lymphoma Mo-MLV Insertion Region 1) and ubiquitinates lysine 119 of histone 3 (H3K119), whereas the PRC2 complex, containing EZH2 (enhancer of zeste homolog 2), catalyzes tri-methylation of lysine 27 of histone 3 (H3K27). Both activities promote durable and heritable locus silencing. Activation in response to certain cellular stresses is thought to promote senescence lead to locus de-repression, likely in part through inhibition of PRC1/2 as well as activation of H3 lysine demethylases and deubiquitinases. Abbreviations: PRC1, protein regulator of cytokinesis 1; PCR2, protein regulator of cytokinesis 1; INK4, inhibitor of cyclin-dependent kinase 4; ARF, alternate reading frame.