Diagenode

MAP Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7.


Wu HA, Balsbaugh JL, Chandler H, Georgilis A, Zullow H, Shabanowitz J, Hunt DF, Gil J, Peters G, Bernstein E

Cbx7 is one of five mammalian orthologs of the Drosophila Polycomb (Pc). Cbx7 recognizes methylated lysine residues on the histone H3 tail and contributes to gene silencing in the context of the Polycomb Repressive Complex 1 (PRC1). However, our knowledge of Cbx7 post-translational modifications remains limited. Through combined biochemical and mass spectrometry approaches, we report a novel phosphorylation site on mouse Cbx7 at residue threonine 118 (T118), near the highly conserved Pc box. The generation of a site-specific antibody to Cbx7T118ph demonstrates that Cbx7 is phosphorylated via MAP kinase signaling. Furthermore, we find Cbx7T118 phosphorylation in murine mammary carcinoma cells, which can be blocked by MEK inhibitors. Upon EGF stimulation, Cbx7 interacts robustly with other members of PRC1. To test the role of Cbx7T118 phosphorylation in gene silencing, we employed a RAS-induced senescence model system. We demonstrate that Cbx7T118 phosphorylation moderately enhances repression of its target gene p16. In summary, we have identified and characterized a novel MAPK-mediated phosphorylation site on Cbx7 and propose that mitogen signaling to the chromatin template regulates PRC1 function.

Tags
Bioruptor
Chromatin Shearing
ChIP-qPCR

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Published
November, 2013

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