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

doi:10.7554/eLife.45205

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

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Abstract

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.

Original language	English
Article number	45205
Number of pages	27
Journal	eLife
Volume	8
DOIs	https://doi.org/10.7554/eLife.45205
Publication status	Published - 14-Jun-2019

Keywords

SELF-RENEWAL
PROTEASOME INHIBITORS
PROTEOMICS ANALYSIS
MISFOLDED PROTEINS
HISTONE H2A
C-MYC
CELLS
NUCLEAR
UBIQUITIN
STRESS

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Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shockFinal publisher's version, 8.13 MBLicence: CC BY

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@article{26713032c5694311bd87eafa99dcc4d6,

title = "Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock",

abstract = "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.",

keywords = "SELF-RENEWAL, PROTEASOME INHIBITORS, PROTEOMICS ANALYSIS, MISFOLDED PROTEINS, HISTONE H2A, C-MYC, CELLS, NUCLEAR, UBIQUITIN, STRESS",

author = "Maria Azkanaz and {Rodr{\'i}guez L{\'o}pez}, Aida and {de Boer}, Bauke and Wouter Huiting and Pierre-Olivier Angrand and Edo Vellenga and Kampinga, {Harm H} and Steven Bergink and Martens, {Joost Ha} and Schuringa, {Jan Jacob} and {van den Boom}, Vincent",

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doi = "10.7554/eLife.45205",

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T1 - Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock

AU - Azkanaz, Maria

AU - Rodríguez López, Aida

AU - de Boer, Bauke

AU - Huiting, Wouter

AU - Angrand, Pierre-Olivier

AU - Vellenga, Edo

AU - Kampinga, Harm H

AU - Bergink, Steven

AU - Martens, Joost Ha

AU - Schuringa, Jan Jacob

AU - van den Boom, Vincent

PY - 2019/6/14

Y1 - 2019/6/14

N2 - 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.

AB - 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.

KW - SELF-RENEWAL

KW - PROTEASOME INHIBITORS

KW - PROTEOMICS ANALYSIS

KW - MISFOLDED PROTEINS

KW - HISTONE H2A

KW - C-MYC

KW - CELLS

KW - NUCLEAR

KW - UBIQUITIN

KW - STRESS

U2 - 10.7554/eLife.45205

DO - 10.7554/eLife.45205

M3 - Article

C2 - 31199242

SN - 2050-084X

VL - 8

JO - eLife

JF - eLife

M1 - 45205

ER -

Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock

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Keywords

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