Glutamine activates heat shock transcription factor‐1 (HSF1) gene transcription

Abstract

We have demonstrated that glutamine (GLN) enhances cytoprotective heat shock protein (HSP) expression. Heat shock transcription factor‐1 (HSF1) is the master regulator for HSP gene expression. We are aimed to explore GLN's effects on HSF1's activity and expression. Non‐stressed or heat‐stressed YAMC colonic epithelial cells were exposed to GLN at 0, 0.5 or 2mM. HSF1 expression, nuclear localization, trimerization and DNA binding were determined. HSF1 promoter‐driven reporter assay and deletion analysis of HSF1 gene promoter were conducted. GLN upregulated HSF1's transactivation activity by increasing its trimerization, nuclear localization and DNA binding. Further, GLN increased HSF1 protein and mRNA expression in both non‐stressed and stressed cells. Deletion analysis of HSF1 promoter shows that the key cis‐ element responsible for GLN response is present between bp −331 to −200. Within this region, deletion of the putative CCAAT enhancer binding protein (C/EBP) binding site resulted in decreased GLN response. In absence of glutamine, HSF1 expression was de‐repressed in C/EBPβ‐silenced cells. Over‐expression of the inhibitory dominant‐negative isoform of C/EBPβ repressed HSF1 expression in presence of adequate glutamine. We for the first time show that GLN not only activates HSF1's transactivation activity, but also activates HSF‐1 gene transcription per se in a C/EBPβ‐dependent manner.