Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation

• DOI: 10.1016/j.molcel.2014.12.020
• Publication Date: 2015-01-22T18:04:39Z
• Authors: Serena Sanulli; Neil Justin; Aurélie Teissandier; Katia Ancelin; Manuela Portoso; Matthieu Caron; Audrey Michaud; Berangère Lombard; Simao T. da Rocha; John Offer; Damarys Loew; Nicolas Servant; Michel Wassef; Fabienne Burlina; Steve J. Gamblin; Edith Heard; Raphaël Margueron
• Keywords: Methylation; Article; Cell Line; Histones; 03 medical and health sciences; Animals; Drosophila Proteins; Humans; Enhancer of Zeste Homolog 2 Protein; Molecular Biology; Embryonic Stem Cells; Mice, Knockout; 0303 health sciences; Models, Genetic; [CHIM.ORGA]Chemical Sciences/Organic chemistry; Lysine; Polycomb Repressive Complex 2; Cell Differentiation; Cell Biology; Histone-Lysine N-Methyltransferase; Chromatin; Drosophila melanogaster; HEK293 Cells; Mutation; Female; RNA Interference

Polycomb Group (PcG) proteins maintain transcriptional repression throughout development, mostly by regulating chromatin structure. Polycomb Repressive Complex 2 (PRC2), a component of the Polycomb machinery, is responsible for the methylation of histone H3 lysine 27 (H3K27me2/3). Jarid2 was previously identified as a cofactor of PRC2, regulating PRC2 targeting to chromatin and its enzymatic activity. Deletion of Jarid2 leads to impaired orchestration of gene expression during cell lineage commitment. Here, we reveal an unexpected crosstalk between Jarid2 and PRC2, with Jarid2 being methylated by PRC2. 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.