Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion

Maintenance of protein homeostasis, through inducible expression of molecular chaperones, is essential for cell survival under protein-damaging conditions. The expression and DNA-binding activity of heat shock factor 2 (HSF2), a member of the heat shock transcription factor family, increase upon exposure to prolonged proteotoxicity. Nevertheless, the specific roles of HSF2 and the global HSF2-dependent gene expression profile during sustained stress have remained unknown. Here, we found that HSF2 is critical for cell survival during prolonged proteotoxicity. Strikingly, our RNA sequencing (RNA-seq) analyses revealed that impaired viability of HSF2-deficient cells is not caused by inadequate induction of molecular chaperones but is due to marked downregulation of cadherin superfamily genes. We demonstrate that HSF2-dependent maintenance of cadherin-mediated cell-cell adhesion is required for protection against stress induced by proteasome inhibition. This study identifies HSF2 as a key regulator of cadherin superfamily genes and defines cell-cell adhesion as a determinant of proteotoxic stress resistance

Immediate perturbation of DNA methylation upon acute prenatal alcohol exposure in the mouse developing brain cortex

Funding information VM was funded by the Agence Nationale de la Recherche « HSF-EPISAME », SAMENTA ANR-13-SAMA-0008-01) and CNRS. AD was supported by a Doctoral Fellowship from the French Ministère de l'Enseignement Supérieur, de la Recherche et de l'Innovation (MESRI) and FM from a Doctoral Fellowship from the CNRS. This study contributes to the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its "Investments for the Future" program. DSD benefited from a CNRS Délégation de Recherche (2018-2020). OTT benefited from travel grants from Université Paris Diderot