Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock
Maria Azkanaz,
Aida Rodríguez López,
Bauke de Boer,
Wouter Huiting,
Pierre-Olivier Angrand,
Edo Vellenga,
Harm H Kampinga,
Steven Bergink,
Joost HA Martens,
Jan Jacob Schuringa,
Vincent van den Boom
Affiliations
Maria Azkanaz
Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Aida Rodríguez López
Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Bauke de Boer
Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Wouter Huiting
Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Pierre-Olivier Angrand
Cell Plasticity & Cancer, Inserm U908, University of Lille, Lille, France
Edo Vellenga
Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Harm H Kampinga
Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Steven Bergink
Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Joost HA Martens
Department of Molecular Biology, Faculty of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, Netherlands
Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Maintenance of epigenetic modifiers is of utmost importance to preserve the epigenome and consequently appropriate cellular functioning. Here, we analyzed Polycomb group protein (PcG) complex integrity in response to heat shock (HS). Upon HS, various Polycomb Repressive Complex (PRC)1 and PRC2 subunits, including CBX proteins, but also other chromatin regulators, are found to accumulate in the nucleolus. In parallel, binding of PRC1/2 to target genes is strongly reduced, coinciding with a dramatic loss of H2AK119ub and H3K27me3 marks. Nucleolar-accumulated CBX proteins are immobile, but remarkably both CBX protein accumulation and loss of PRC1/2 epigenetic marks are reversible. This post-heat shock recovery of pan-nuclear CBX protein localization and reinstallation of epigenetic marks is HSP70 dependent. Our findings demonstrate that the nucleolus is an essential protein quality control center, which is indispensable for recovery of epigenetic regulators and maintenance of the epigenome after heat shock.
