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Jarid2 methylation via the PRC2 complex regulates H3K27me3 deposition during cell differentiation

DOI: 10.1016/j.molcel.2014.12.020 DOI Help
PMID: 25620564 PMID Help

Authors: Serena Sanulli (Institut Curie) , Neil Justin (MRC National Institute for Medical Research) , Aurélie Teissandier (Institut Curie) , Katia Ancelin (Institut Curie) , Manuela Portoso (Institut Curie) , Matthieu Caron (Institut Curie) , Audrey Michaud (Institut Curie) , Berangère Lombard (Institut Curie) , Simao t. Da rocha (Institut Curie) , John Offer (MRC National Institute for Medical Research) , Damarys Loew (Institut Curie) , Nicolas Servant (Institut Curie) , Michel Wassef (Institut Curie) , Fabienne Burlina (Sorbonnes Universite´ s) , Steven Gamblin (National Institute for Medical Research, Medical Research Council) , Edith Heard (Institut Curie) , Raphaël Margueron (Institut Curie)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 57 (5) , PAGES 769 - 783

State: Published (Approved)
Published: March 2015
Diamond Proposal Number(s): 9826

Open Access Open Access

Abstract: 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.

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography

Added On: 30/03/2015 13:26

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)