Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation.
Bottom Line: This modification is recognized by the Eed core component of PRC2 and triggers an allosteric activation of PRC2's enzymatic activity.We show that Jarid2 methylation is important to promote PRC2 activity at a locus devoid of H3K27me3 and for the correct deposition of this mark during cell differentiation.Our results uncover a regulation loop where Jarid2 methylation fine-tunes PRC2 activity depending on the chromatin context.
Affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.Show MeSH
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Mentions: To test whether Jarid2 is methylated in vivo, we generated antibodies recognizing both Jarid2 di-methylated and tri-methylated at K116 (Jarid2-K116me2 and Jarid2-K116me3). We verified the specificity of these antibodies by dot blot on peptides and by western blot on in vitro methylated recombinant proteins (Figures S2A, S2B, and S2C). Western blot on nuclear extract of ESC line (E14) showed a robust signal, both for the di- and tri-methylated Jarid2-K116 antibodies, which was completely lost in ESC constitutively knocked out (KO) for Eed or conditionally KO for Ezh2 (SET domain deletion) (Figure 2A). We additionally performed competition experiment with Jarid2-K116 me2 and me3 peptides and showed that the signal for Jarid2 tri-methylation was competed out by the Jarid2-K116me3 peptide but not by Jarid2-K116me2 peptide (Figure 2B).
Affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.