Expression of mRNAs for two novel isoforms of mouse heat shock factor 1 in mouse cells and tissues

Abstract

Heat shock transcription factor 1 (HSF1) mediates the response to heat in all cellular organisms. On exposure to heat, the HSF1 in cells refolds, enters the nucleus and switches on genes encoding protective heat shock proteins (hsps). Two isoforms of mammalian HSF1, denoted α and β, were previously known to be derived by alternate splicing of an additional coding exon. These forms differ by the presence of an additional 22 amino acid segment in the HSF1α protein as compared to β. Our previous studies show that these isoforms switch on different subsets of hsp genes and to different extents; HSF1α is generally a better activator of hsp genes. This study provides evidence for expression of the mouse mRNAs for two additional isoforms, also derived by alternate splicing, containing an additional 28 amino acid segment, denoted HSF1γ and δ. Existence of these new isoforms was predicted by bioinformatic analysis of HSF1 expressed sequence tags using the basic local alignment search tool (BLAST). Comparative bioinformatic analysis suggests many vertebrate species, including zebrafish, clawed frogs, mice, and humans possess these isoforms. Based on reverse‐transcriptase PCR analysis, the HSF1γ isoform mRNAs from mouse fibroblast cells and various mouse tissues may be widely expressed, both before and after heat shock, while HSF1δ is expressed only in certain tissues. Experiments are underway to construct mouse expression plasmids that can be used to test the ability of HSF1γ and δ isoforms to activate hsp target genes in mouse fibroblasts to begin to identify their functions. Supported by NIH NIGMS grant 1 R15 GM096231–01.