Dynamic behavior of the epigenetic machinery upon thermal stress

Maintenance of the epigenome is of utmost importance to warrant appropriate cellular functioning Here we analyzed PRC1/2 function, in response to cellular stress. We observe that heat shock (HS) leads to nucleolar accumulation of CBX proteins, and are strongly immobilized in a 1,6-hexanediol insensitive manner, suggestive of a HS-induced liquid-to-solid phase transition of the nucleolus. CBX protein recovery from the nucleolus is dependent on heat shock protein (HSP) activity. LC-MS/MS analyses of nucleoli shows HS-induced nucleolar accumulation of PRC1/2 subunits, various chromatin regulators, HSPs, and the 26S proteasome. Finally, we find that HS leads to a strong reduction of PRC1/2 chromatin binding at target genes and loss of H2AK119ub and H3K27me3. Our findings demonstrate that thermal stress results in a rapid accumulation of epigenetic regulators in the nucleolus, and a concomitant loss of PRC1/2 complex chromatin binding and associated epimarks, underlining that environmental stress directly alters the epigenome. Overall design: ChIP-seq analysis of CBX proteins using control and Heatshock induced cells was performed using illumina high-throughput sequencing